22-Thiavitamin D3 derivatives

ABSTRACT

Compounds of the general formula: ##STR1## wherein R 1  represents a C1-10 alkyl group which may be substituted by one or more hydroxyl groups, R 2  represents a hydrogen atom or a hydroxyl group, and R 3  represents a hydrogen atom or a hydroxyl group; their intermediates; as well as synthesis processes of these compounds and intermediates are disclosed. The compounds of this invention, vitamin D derivatives substituted by sulfur atoms at the 22-position have a strong inhibitory effect against proliferation of keratinocytes.

This application is a 371 of PCT/JP95/00699 filed Apr. 10, 1995.

1. Field of the Invention

This invention relates to novel vitamin D₃ derivatives. Morespecifically, this invention relates to vitamin D₃ derivativessubstituted by sulfur atoms at the 22-position and processes forpreparing said derivatives. This invention also relates to intermediateswhich are useful for preparing said compounds and processes forpreparing said intermediates.

2. Description of the Prior Art

Active-type vitamin D₃ is known to have many physiological activitiesincluding calcium metabolism regulation, differentiation induction,immunoregulation, etc.

In recent years, physiological activities of D vitamins have beengradually illuminated. D vitamins, such as 1α,25-dihydroxyvitamin D₃,are known to exhibit a wide range of physiological activities includingcalcium metabolism regulation, proliferation inhibition ordifferentiation induction of oncocytes or the like, immunoregulation,etc. However, 1α,25-dihydroxyvitamin D₃ is not suitable for use as, forexample, antineoplastic, antirheumatic, etc., because itdisadvantageously causes hypercalcemia after long-term and continuousadministration. Thus, a number of vitamin D derivatives have recentlybeen synthetized in order to divide these activities of D vitamins, andtheir physiological activities have been investigated.

One example of such derivatives is1α,3β-dihydroxy-20(S)-(3-hydroxy-3-methylbutyloxy-9,10-secopregna-5,7,10(19)-trienewhich is a derivative of vitamin D₃ substituted by an oxygen atom at the22-position, disclosed in JPA (Unexamined Japanese Patent Application)61-267550 (1986).

DISCLOSURE OF THE INVENTION

After profound study on vitamin D derivatives, the inventors of thisinvention found that vitamin D derivatives substituted by sulfur atomsat the 22-position have a strong inhibitory effect against proliferationof keratinocytes.

This invention relates to 22-thiavitamin D derivatives of the followinggeneral formula (I): ##STR2## wherein R₁ represents a C1-10 alkyl groupwhich may be substituted by one or more hydroxyl groups, R₂ represents ahydrogen atom or a hydroxyl group, and R₃ represents a hydrogen atom ora hydroxyl group; and processes for preparing said derivatives.

This invention also relates to synthetic intermediates which are usefulfor preparing the compounds of the general formula (I) and processes forpreparing said intermediates.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing an inhibitory effect against proliferation ofhuman keratinocytes at each concentration of 1α,25-dihydroxyvitamin D₃ ;

FIG. 2 is a graph showing an inhibitory effect against proliferation ofhuman keratinocytes at each concentration of the compound of Example 88;

FIG. 3 is a graph showing an inhibitory effect against proliferation ofhuman keratinocytes at each concentration of 1α,25-dihydroxyvitamin D₃ ;

FIG. 4 is a graph showing an inhibitory effect against proliferation ofhuman keratinocytes at each concentration of the compound of Example 33;and

FIG. 5 is a graph showing an inhibitory effect against proliferation ofhuman keratinocytes at each concentration of the compound of Example 35.

THE BEST EMBODIMENTS OF THE INVENTION

As described above, this invention provides 22-thiavitamin D derivativesof the following general formula (I): ##STR3## wherein R₁ represents aC1-10 alkyl group which may be substituted by one or more hydroxylgroups, R₂ represents a hydrogen atom or a hydroxyl group, and R₃represents a hydrogen atom or a hydroxyl group.

In the compounds of the general formula (I), R₃ is preferably a hydroxylgroup. R₁ is preferably a C1-10 alkyl group substituted by one or morehydroxyl groups, and more preferably a group of the following generalformula (III): ##STR4## wherein R₄ and R₅, which may be the same ordifferent, each represents a hydrogen atom or a hydroxyl group providedthat the both are not hydroxyl groups, m represents an integer of 1through 4, and n represents an integer of 0 through 2. More preferably,R₄ and R₅ are hydrogen atoms.

The steric configuration of the general formula (I) is not specificallylimited, but preferably corresponds the general formula (II): ##STR5##wherein R₁ represents a C1-10 alkyl group which may be substituted byone or more hydroxyl groups, and R₂ represents a hydrogen atom or ahydroxyl group.

This invention also relates to processes for preparing vitamin D₃derivatives substituted by sulfur atoms at the 22-position. Accordingly,this invention relates to a process for preparing a compound of thegeneral formula (XVI): ##STR6## wherein R₂₅ represents a C1-10 alkylgroup which may be substituted by one or more hydroxyl groups, R₂₆ andR₂₇, which may be the same or different, each represents a hydrogen atomor a protective group, and R₂₈ represents a hydrogen atom or a hydroxylgroup, by subjecting a compound of the general formula (XV): ##STR7##wherein R₂₅ represents a C1-10 alkyl group which may be substituted byone or more hydroxyl groups, R₂₆ and R₂₇, which may be the same ordifferent, each represents a hydrogen atom or a protective group, andR₂₈ represents a hydrogen atom or a hydroxyl group, to a lightirradiation and thermal isomerization reaction.

This invention also provides synthetic intermediates which are usefulfor preparing the compounds of the general formula (I) and processes forpreparing said intermediates.

Representative examples of the synthetic intermediates include, forexample,

compounds of the general formula (VI): ##STR8## wherein R₆ and R₇, whichmay be the same or different, each represents a hydrogen atom or aprotective group, and R₈ represents a C1-10 alkyl group which may besubstituted;

compounds of the general formula (XI): ##STR9## wherein R₁₅ and R₁₆,which may be the same or different, each represents a hydrogen atom or aprotective group, and A₁ represents --CHOH-- or --CO--; and

compounds of the general formula (XIII): ##STR10## wherein R₁₉ and R₂₀,which may be the same or different, each represents a hydrogen atom or aprotective group, R₂₁ represents a C1-10 alkyl group which may besubstituted, and A₃ represents --CHOH-- or --CO--.

Especially preferred examples of the synthetic intermediates include,for example,

compounds of the general formula (X): ##STR11## wherein R₁₂ and R₁₃,which may be the same or different, each represents a hydrogen atom or aprotective group, and R₁₄ represents a C1-10 alkyl group which may besubstituted;

compounds of the general formula (XII): ##STR12## wherein R₁₇ and R₁₈,which may be the same or different, each represents a hydrogen atom or aprotective group, and A₂ represents --CHOH-- or --CO--; and

compounds of the general formula (XIV): ##STR13## wherein R₂₂ and R₂₃,which may be the same or different, each represents a hydrogen atom or aprotective group, R₂₄ represents a C1-10 alkyl group which may besubstituted, and A₄ represents --CHOH-- or --CO--.

Each of R₈, R₁₁, R₁₄, R₂₁ and R₂₄ is preferably a C1-10 alkyl groupsubstituted by one or more hydroxyl groups, more preferably a group ofthe general formula (III): ##STR14## wherein R₄ and R₅, which may be thesame or different, each represents a hydrogen atom or a hydroxyl groupprovided that the both are not hydroxyl groups, m is an integer of 1through 4 and n is an integer of 0 through 2, and most preferably agroup of the general formula (III) wherein R₄ and R₅ are hydrogen atoms.

For the purpose of this invention, the C1-10 alkyl group which may besubstituted by hydroxyl groups represents a straight or branched chainalkyl group such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl,s-butyl, t-butyl, pentyl, hexyl, heptyl, octyl, nonyl and decanylgroups. Preferable examples are 3-methylbutyl, 3-ethylpentyl,4-methylpentyl, 3-(n-propyl)hexyl, 4-ethylhexyl, 5-methylhexyl,6-methylheptyl, 5-ethylheptyl and 4-(n-propyl)heptyl groups, morepreferably 3-methylbutyl, 3-ethylpentyl and 4-methylpentyl groups.

In the C1-10 alkyl which may be substituted by one or more hydroxylgroups, the number of hydroxyl substituents is for example, 0, 1, 2, 3,preferably 1 or 2, more preferably 1.

Examples of the C1-10 alkyl group substituted by one or more hydroxylgroups include 3-hydroxy-3-methylbutyl, 2-hydroxy-3-methylbutyl,4-hydroxy-3-methylbutyl, 2,3-dihydroxy-3-methylbutyl,2,4-dihydroxy-3-methylbutyl, 3,4-dihydroxy-3-methylbutyl,3-hydroxy-3-ethylpentyl, 2-hydroxy-3-ethylpentyl,4-hydroxy-3-ethylpentyl, 2,3-dihydroxy-3-ethylpentyl,2,4-dihydroxy-3-ethylpentyl, 3,4-dihydroxy-3-ethylpentyl,4-hydroxy-4-methylpentyl, 3-hydroxy-4-methylpentyl,5-hydroxy-4-methylpentyl, 3,4-dihydroxy-4-methylpentyl,3,5-dihydroxy-4-methylpentyl, 4,5-dihydroxy-4-methylpentyl,3-hydroxy-3-(n-propyl)hexyl, 4-hydroxy-3-(n-propyl)hexyl,2-hydroxy-3-(n-propyl)hexyl, 2,3-dihydroxy-3-(n-propyl)hexyl,3,4-dihydroxy-3-(n-propyl)hexyl, 2,4-dihydroxy-3-(n-propyl)hexyl,3-hydroxy-4-ethylhexyl, 4-hydroxy-4-ethylhexyl, 5-hydroxy-4-ethylhexyl,3,4-dihydroxy-4-ethylhexyl, 3,5-dihydroxy-4-ethylhexyl,4,5-dihydroxy-4-ethylhexyl, 4-hydroxy-5-methylhexyl,5-hydroxy-5-methylhexyl, 6-hydroxy-5-methylhexyl,4,5-dihydroxy-5-methylhexyl, 4,6-dihydroxy-5-methylhexyl,5,6-dihydroxy-5-methylhexyl, 5-hydroxy-6-methylheptyl,6-hydroxy-6-methylheptyl, 7-hydroxy-6-methylheptyl,5,6-dihydroxy-6-methylheptyl, 5,7-dihydroxy-6-methylheptyl,6,7-dihydroxy-6-methylheptyl, 4-hydroxy-5-ethylheptyl,5-hydroxy-5-ethylheptyl, 6-hydroxy-5-ethylheptyl,4,5-dihydroxy-5-ethylheptyl, 4,6-dihydroxy-5-ethylheptyl,5,6-dihydroxy-5-ethylheptyl, 3-hydroxy-4-(n-propyl)heptyl,4-hydroxy-4-(n-propyl)heptyl, 5-hydroxy-4-(n-propyl)heptyl,3,4-dihydroxy-4-(n-propyl)heptyl, 3,5-dihydroxy-4-(n-propyl)heptyl and4,5-dihydroxy-4-(n-propyl)heptyl groups, preferably3-hydroxy-3-methylbutyl, 2,3-dihydroxy-3-methylbutyl,3,4-dihydroxy-3-methylbutyl, 3-hydroxy-3-ethylpentyl,2,3-dihydroxy-3-ethylpentyl, 3,4-dihydroxy-3-ethylpentyl,4-hydroxy-4-methylpentyl, 3,4-dihydroxy-4-methylpentyl and4,5-dihydroxy-4-methylpentyl groups, more preferably3-hydroxy-3-methylbutyl, 3-hydroxy-3-ethylpentyl and4-hydroxy-4-methylpentyl groups.

The protective group in this invention includes acyl, substituted silyl,substituted alkyl groups or the like, preferably acyl and substitutedsilyl groups.

The acyl group in this invention means a formyl group, a loweralkylcarbonyl group which may be substituted, an arylcarbonyl groupwhich may be substituted, an aralkylcarbonyl group which may besubstituted, a lower alkyloxycarbonyl group which may be substituted, anaryloxycarbonyl group which may be substituted or an aralkyloxycarbonylgroup which may be substituted, preferably a formyl group, a loweralkylcarbonyl group, a phenylcarbonyl group which may be substituted, alower alkyloxycarbonyl group, a phenylalkyloxycarbonyl group which maybe substituted, more preferably formyl, acetyl, propionyl, butyryl,pivaloyl, benzoyl, ethoxycarbonyl, t-butoxycarbonyl, benzyloxycarbonylgroups.

The substituted silyl group means a silyl group which is substituted byone or more lower alkyl groups which may be substituted or aryl groupswhich may be substituted, etc., preferably a tri-substituted silylgroup. Preferable examples of the substituted silyl group includetrimethylsilyl, triethylsilyl, triisopropylsilyl, t-butyldiphenylsilyland t-butyldimethylsilyl groups.

The substituted alkyl group means an alkyl group substituted by one ormore substituents. Preferable examples of the substituent are an arylgroup which may be substituted, an alkyloxy group which may besubstituted, etc., especially an alkyloxy group which may be substitutedby an alkyloxy or other group. The alkyloxy group which may besubstituted by an alkyloxy or other group includes, for example,methoxymethyl, 2-methoxyethoxymethyl and tetrahydropyran-2-yl groups.

The protective group for each of R₆, R₇, R₁₂, R₁₃ is preferably stableunder acidic conditions, more preferably an acyl group, most preferablyan acetyl group. The protective group for each of R₉, R₁₀, R₁₅, R₁₆,R₁₇, R₁₈, R₁₉, R₂₀, R₂₂, R₂₃ is preferably a substituted silyl group,more preferably trimethylsilyl, triethylsilyl, triisopropylsilyl,t-butyldimethylsilyl and t-butyldiphenylsilyl groups, more preferablyt-butyldimethylsilyl group.

The reducing conditions in this invention mean that a reducing agentexists in the reaction system, said reducing agent including borane,trialkylsilane, preferably trialkylsilane, more preferablytriethylsilane.

The basic conditions in this invention mean that a base which may form athioalcoholate exists in the reaction system, said base includingpotassium hydroxide, sodium hydroxide, sodium tetraborate, preferablysodium tetraborate.

The substituents in this invention include, for example, a halogen atom,and cyano, nitro, hydroxyl, alkoxy, amino, mercapto and acyloxy groups.

Especially preferable examples of the substituents in R₈, R₁₁, R₁₄, R₂₁,R₂₄ are, for example, hydroxyl, alkoxy and acyloxy groups, mostpreferably a hydroxyl group.

The compounds of this invention have a strong inhibitory effect againstproliferation of keratinocytes. In the compounds of this invention, thesteric configuration at the 20-position and the steric configuration ofhydroxyl groups may be either R or S, or either α or β.

The compounds of this invention are preferably substituted at the1-position by a hydroxyl group which is preferably in α-configuration.

All the compounds of this invention are novel and synthesized asdescribed below, for example.

The thiol which is used as a starting material for synthesis of sidechains from the 22-position was synthesized by the process described inJPA-5-505613 (1993) or the process of the following Scheme 1: ##STR15##wherein X represents a halogen atom, j represents an integer of 0through 2 and k represents an integer of 2 through 5.

Namely, it is obtained by starting with a halogenated ester and reactingit with 1) a metal salt of a thiocarboxylic acid such as potassiumthioacetate, and 2) a Grignard reagent. It may also be obtained byreacting the starting material with 2) at first and then 1), andhydrolyzing thus obtained compound under reducing or alkali conditions.

The compounds of the general formula (I) wherein R₂ represents ahydrogen atom are synthesized by the process of the following Scheme 2,for example: ##STR16## wherein R₂₉ represents a C1-10 alkyl group whichmay be substituted.

In Scheme 2, the starting compound (6) is synthesized by, for example,the process of Murayama et al. (Bioorg. Med. Chem. Lett. 2, 1289(1992)). The hydroxyl group of this compound (6) is deprotected andthereafter reprotected by an acyl group, preferably an acetyl group, togive the compound (8). This compound (8) is subjected to a reductivethiolation reaction to give the compound (9). The reductive thiolationis carried out, for example, by using boron trifluoride-ether complex orboron trifluoride monohydrate/triethylsilane, or trifluoroaceticacid/borane-pyridine complex, preferably by using borontrifluoride-ether complex/triethylsilane.

The solvent used in this reaction includes, for example, halogenoussolvents, ethereal solvents, aromatic hydrocarbonaceous solvents,preferably halogenous solvents, more preferably, dichloromethane.

The reaction temperature depends on the nature of the compound used, thereagent and other factors, but generally corresponds to a temperature atwhich 5,7-diene moiety is not isomerized, preferably between -30° C. androom temperature, more preferably around 0° C.

The reaction time depends on the reagent used, the amount of thecompound and other factors, but generally ranges from 1 to 12 hours,preferably 3 to 10 hours, more preferably 5 to 7 hours.

Then, the compound (9) obtained as above is deprotected in aconventional manner, and optionally after separation of diastereomers,subjected to a light irradiation and thermal isomerization reaction togive the compound (12). If it is difficult to separate diastereomers inthis step, the protective group of the hydroxyl group at either one orthe both of the 1- and 3-positions may be converted into an appropriateprotective group according to the necessity to allow them to beseparated.

The compounds of the general formula (I) wherein R₂ represents ahydroxyl group are synthesized by, for example, the process of thefollowing Scheme 3: ##STR17##

In Scheme 3, the starting compound (13) is synthesized by, for example,the process of Murayama et al. (Chem. Pharm. Bull. 34, 4410 (1986)). Atfirst, an oxygen functional group is introduced into the 16-position ofthe compound (13). The oxygen functional group is introduced by, forexample, using 2-(phenylsulfonyl)-3-phenyloxazylidine in the presence ofa base, or introducing a halogen into the 16-position and thenconverting it into a hydroxyl group, preferably by using2-(phenylsulfonyl)-3-phenyloxazylidine in the presence of a base. Thebase used here includes metal alkoxides, metal amides, metal hydrides,etc., preferably metal alkoxides, more preferably potassium t-butoxide.

The compound (14) obtained as above is subjected to a Wittig-typereaction to give the compound (15) consisting of an E, Z mixture, whichis then converted into the compound (16) by oxidation reaction. Thisreaction may be an ordinary oxidation reaction using chromate, dimethylsulfoxide, etc., preferably an oxidation reaction using dimethylsulfoxide. If the E, Z mixture of the compound (15) is oxidized bymanganese dioxide in this step, only the reaction of the E-isomerproceeds to yield the compound (16) consisting of the E-isomer. Theunreacted Z-isomer of the compound (15) can be stereoselectively led tothe compound (16) consisting of the Z-isomer by Swern oxidation or thelike as shown in the following Scheme 4. ##STR18##

The E-isomer of the compound (15) can also be synthesized by the processof the following Scheme 5. ##STR19##

The starting compound (17) in Scheme 5 can be synthesized by, forexample, the process of Murayama et al. (Chem. Pharm. Bull. 34, 4410(1986)). The 5,7-diene moiety of the compound (17) is protected by aprotective group such as 4-phenyl-1,2,4-triazoline-3,5-dione, thereafteroxidized by an oxidizing agent such as selenium dioxide, chromic acid,manganese (III) acetate, preferably selenium dioxide, and deprotected togive the E-isomer of the compound (15).

The compound (16) obtained by the process described above is convertedinto the compound (20) by 1,4-addition of various thiols as shown in thefollowing Scheme 6: ##STR20## wherein R₃₀ represents a C1-10 alkyl groupwhich may be substituted.

This reaction can be effected by applying an ordinary 1,4-additionreaction for α,β-unsaturated ketones. This reaction may be carried out,for example, under basic conditions, preferably by using sodiumhydroxide, sodium tetraborate, more preferably sodium tetraborate.

The solvent used here depends on the reagent used and other factors.When sodium tetraborate is used, the solvent is an ethereal or alcoholicsolvent used alone or as mixture with water, preferably a mixed solventof an ethereal solvent and water, more preferably a mixed solvent oftetrahydrofuran and water.

The reaction temperature depends on the reagent used and other factors,but generally ranges from -20° to 60° C., preferably 0° to 40° C., morepreferably 15° to 25° C.

The reaction time depends on the reagent used, the amount of thecompound and other factors, but generally ranges from 3 to 24 hours,preferably 9 to 15 hours, more preferably 12 to 15 hours.

The compound (20) obtained as above can be converted into the compound(23) through reduction, deprotection, light irradiation and thermalisomerization in a conventional manner.

The following examples further explain this invention in detail, but arenot intended to limit the scope of this invention.

EXAMPLE 1 4-Ethyl-4-hydroxy-1-hexanethiol

To acetone (30 ml) were added 4-bromobutyric acid ethyl ester (1.5 ml,10.5 mmol) and potassium thioacetate (1.8 g, 15.8 mmol), and the mixturewas stirred at room temperature for 30 minutes and then filtered, andthe solids were washed with acetone. The filtrate was concentrated, andthen purified by column chromatography on silica gel (hexane:ethylacetate=5:1) to give 4-acetylthiobutyric acid ethyl ester (2.03 g).Then, ethyl magnesium bromide (1.04M solution in tetrahydrofuran, 31.3ml, 32.6 mmol) in dry tetrahydrofuran (8 ml) was cooled to 0° C. underan argon atmosphere, and a solution of 886 mg of the compound obtainedas above in dry tetrahydrofuran (4 ml) was added dropwise and themixture was stirred at room temperature for 2 hours. The reactionmixture was quenched with an aqueous saturated ammonium chloridesolution, acidified with 10% hydrochloric acid and extracted with ethylacetate. The extract was washed with brine and dried over magnesiumsulfate. The solvent was distilled off under reduced pressure and theresidue was purified by column chromatography on silica gel(hexane:ethyl acetate=4:1) to give the title compound (221 mg, 2 steps,29%).

IR(neat): 3450, 2950, 2550, 1460, 1370, 1240, 1170 cm⁻¹.

¹ H NMR(60 MHz) δ: 2.47(t,2H), 1.74-1.08(m,8H), 0.84(t,6H).

EXAMPLE 2 5-Hydroxy-5-methyl-1-hexanethiol

Under an argon atmosphere, to a solution of methyl magnesium bromide(0.99M solution in tetrahydrofuran, 70 ml, 69.3 mmol) in drytetrahydrofuran (80 ml) was added a solution of ethyl 5-bromovalerate(3.66 ml, 23.1 mmol) in dry tetrahydrofuran (10 ml) dropwise at 0° C.,and the mixture was stirred at room temperature for 1.5 hour, thenquenched with an aqueous saturated ammonium chloride solution, pouredinto water and extracted with ethyl acetate. The extract was washed withbrine and dried over magnesium sulfate. The solvent was distilled offunder reduced pressure to give crude 6-bromo-2-methyl-2-hexanol (5.28g). This crude product was dissolved into acetone (80 ml) and potassiumthioacetate (3.96 g, 34.7 mmol) was added. The mixture was stirred atroom temperature for 1.5 hour and filtered, then the filtrate wasconcentrated under reduced pressure. The residue was purified by columnchromatography on silica gel (hexane:ethyl acetate: 4:1) to give6-acetylthio-2-methyl-2-hexanol (3.75 g). Thus obtained6-acetylthio-2-methyl-2-hexanol was dissolved into tetrahydrofuran (130ml) and lithium aluminum hydride (2.24 g, 59.0 mmol) was added byportions at 0° C. After this suspension was stirred at room temperaturefor 1.5 hour, excessive lithium aluminium hydride was treated with ethylacetate and the reaction solution was acidified with 4N hydrochloricacid. The solution was extracted with ethyl acetate, and the organiclayer was washed with brine, dried over magnesium sulfate, then thesolvent was removed under reduced pressure. The residue was purified bycolumn chromatography on silica gel (hexane:ethyl acetate=4:1) to givethe title compound (2.95 g, 3 steps, 85%).

IR(neat): 3400, 2950, 2550, 1460, 1370, 1240, 1140, 1040 cm⁻¹.

¹ H NMR(60 MHz) δ: 2.47(t,2H), 1.92-1.28(m,6H), 1.18(s,6H).

EXAMPLE 3 6-Hydroxy-6-methyl-1-heptanethiol

The title compound was synthesized from ethyl 6-bromocaproate by thesame procedure as in Example 2.

IR(neat): 3400, 2950, 2550, 1460, 1370, 1240, 1140, 1040 cm⁻¹.

¹ H NMR(60 MHz) δ: 2.47(t,2H), 1.92-1.28(m,8H), 1.18(s,6H).

EXAMPLE 4 3-Hydroxy-3-n-propyl-1-hexanethiol

The title compound was synthesized from ethyl 3-bromopropionate andn-propyl magnesium bromide by the same procedure as in Example 2.

IR(neat): 3450, 2950, 2550, 1460, 1370, 1240, 1150, 1040 cm⁻¹.

¹ H NMR(60 MHz) δ: 2.47(t,2H), 1.94-0.74(m,16H).

EXAMPLE 5 1α,3β-Dihydroxy-20-oxopregna-5,7-diene

Under an argon atmosphere, to a solution of1α,3β-bis(t-butyldimethylsilyloxy)-20-oxopregna-5,7-diene (4.10 g, 7.33mmol) in dry tetrahydrofuran (80 ml), was added tetra-n-butylammoniumfluoride (1M solution in tetrahydrofuran, 74 ml, 74.0 mmol), and themixture was refluxed for 16 hours. Then the mixture was poured intowater and extracted with ethyl acetate. The organic layer was washedsuccessively with 10% hydrochloric acid, an aqueous saturated sodiumbicarbonate solution and brine, and dried over magnesium sulfate. Afterthe solvent was distilled off under reduced pressure, the residue waspurified by column chromatography on silica gel(dichloromethane:ethanol=15:1) to give the title compound (1.68 g, 69%)as a white solid.

IR(neat): 3400, 2930, 1700, 1360, 1050 cm⁻¹.

¹ H NMRδ: 5.73-5.66(m,1H), 5.43-5.36(m,1H), 4.12-3.93(m,1H),3.80-3.73(brs,1H), 2.16(s,3H), 0.93(s,3H), 0.59(s,3H).

MS m/z: 330(M⁺), 251(100%).

UV λ_(max) nm: 271, 283, 294.

EXAMPLE 6 1α,3β-Diacetoxy-20-oxopregna-5,7-diene

A solution of the compound obtained in Example 5 (1.68 g, 5.08 mmol),acetic anhydride (30 ml) and 4-dimethylaminopyridine (DMAP, 60 mg) inpyridine (60 ml) was stirred at room temperature for 4 days. Thereaction mixture was poured into water and extracted with ethyl acetate.The organic layer was washed with brine and dried over magnesiumsulfate. The solvent was distilled off under reduced pressure and theresidue was purified by column chromatography on silica gel(hexane:ethyl acetate=3:1) to give the title compound (1.65 g, 78%) as awhite solid.

IR(neat): 2970, 1740, 1700, 1440, 1360, 1240, 1040 cm⁻¹.

¹ H NMRδ: 5.70-5.60(m,1H), 5.44-5.34(m,1H), 5.07-4.85(m,2H), 2.14(s,3H),2.10(s,3H), 2.04(s,3H), 1.01(s,3H), 0.57(s,3H).

MS m/z: 414(M⁺), 294(100%).

UV λ_(max) nm: 270, 281, 292.

EXAMPLE 71α,3β-Diacetoxy-20-(3-hydroxy-3-methylbutylthio)pregna-5,7-diene(mixture of 20R- and S-isomers)

Under an argon atmosphere, a solution of the compound obtained inExample 6 (100 mg, 0.241 mmol) and 3-methyl-3-hydroxy-1-butanethiol(34.7 mg, 0.289 mmol) in dry dichloromethane (0.5 ml) was cooled to 0°C. and stirred with boron trifluoride-ether complex (35.5 μl, 0.289mmol) for 3 minutes, then stirred with triethylsilane (57.8 μl, 0.362mmol) at 0° C. for 5.5 hours. Then the reaction mixture was poured intowater and extracted with ethyl acetate. The organic layer was washedwith an aqueous saturated sodium bicarbonate solution and brine anddried over magnesium sulfate, then the solvent was removed under reducedpressure. The residue was purified by preparative thin-layerchromatography (2 plates, dichloromethane:ethanol=20:1, developed once)to give the title compound mixture (55.7 mg, 45%) as a colorless oil.The starting material (43.3 mg, 35%) was also recovered.

IR(neat): 3460, 2960, 1740, 1370, 1240, 1030 cm⁻¹.

¹ H NMRδ: 5.70-5.60(m,1H), 5.42-5.32(m,1H), 5.07-4.84(m,2H), 2.09(s,3H),2.03(s,3H), 1.39 and 1.30(d of each diastereomer, J=6.3 and 6.6 Hz, 3H),1.25(s,6H), 1.01(s,3H), 0.69 and 0.65(s of each diastereomer, 3H).

MS m/z: 518(M⁺), 69(100%).

UV λ_(max) nm: 273, 282, 293.

EXAMPLE 81α,3β-Diacetoxy-20(S)-(4-ethyl-4-hydroxyhexylthio)pregna-5,7-diene and1α,3β-diacetoxy-20(R)-(4-ethyl-4-hydroxyhexylthio)pregna-5,7-diene

After the procedure of Example 7 was followed using the compoundobtained in Example 6 (150 mg, 0.361 mmol), the compound obtained inExample 1 (73.0 mg, 0.450 mmol), boron trifluoride-ether complex (55.3μl, 0.450 mmol), dry dichloromethane (1 ml) and triethylsilane (201 μl,1.26 mmol), the residue was purified by preparative thin-layerchromatography (4 plates, dichloromethane:ethyl acetate=9:1, developedonce) to give a mixture of the title compounds (38.8 mg, 19%) as acolorless oil as well as a recovered material1α,3β-diacetoxy-20-oxopregna-5,7-diene (89.4 mg). Thus obtained mixturewas further purified by preparative thin-layer chromatography (4 plates,dichloromethane:ethyl acetate=25:1, developed 5 times) to give the titlecompounds 20S-isomer (8.6 mg, 4%) and 20R-isomer (21.1 mg, 10%) both ascolorless oils.

20S-isomer:

IR(neat): 3500, 2950, 1740, 1460, 1370, 1240, 1030 cm⁻¹.

¹ H NMRδ: 5.69-5.63(m,1H), 5.42-5.35(m,1H), 5.04-4.88(m,2H), 2.09(s,3H),2.04(s,3H), 1.46(q,J=7.3 Hz,4H), 1.38(d,J=6.3 Hz,3H), 1.01(s,3H),0.86(t,J=7.3 Hz,6H), 0.65(s,3H).

MS m/z: 560(M⁺), 143(100%).

UV λ_(max) nm: 270, 281, 293.

20R-isomer:

IR(neat): 3500, 2950, 1740, 1460, 1370, 1240, 1050 cm⁻¹.

¹ H NMRδ: 5.69-5.61(m,1H), 5.40-5.31(m,1H), 5.06-4.97(m,2H), 2.08(s,3H),2.04(s,3H), 1.49(q,J=7.3 Hz,4H), 1.29(d,J=6.6 Hz,3H), 1.01(s,3H),0.86(t,J=7.3 Hz,6H), 0.69(s,3H).

MS m/z: 560(M⁺), 143(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 91α,3β-Diacetoxy-20-(4-hydroxy-4-methylpentylthio)pregna-5,7-diene(mixture of 20R- and S-isomers)

After the procedure of Example 7 was followed using the compoundobtained in Example 6 (200 mg, 0.482 mmol),4-hydroxy-4-methylpentanethiol (77.6 mg, 0.578 mmol), borontrifluoride-ether complex (71.0 μl, 0.578 mmol), dry dichloromethane (1ml) and triethylsilane (115 μl, 0.723 mmol), the residue was purified bypreparative thin-layer chromatography (4 plates, hexane:ethylacetate=1:1, developed once) to give a mixture of the title compounds(93.3 mg, 36%) as a colorless oil as well as a recovered material (133mg).

IR(neat): 3450, 2950, 1740, 1371, 1240, 1030 cm⁻¹.

¹ H NMRδ: 5.70-5.60(m,1H), 5.42-5.32(m,1H), 5.07-4.84(m,2H),2.54(t,J=7.3 Hz,2H), 2.09(s,3H), 2.03(s,3H), 1.39 and 1.29(d of eachdiastereomer, J=7.3 and 6.6 Hz,3H), 1.23(s,6H), 1.01(s,3H), 0.69 and0.65(s of each diastereomer, 3H).

MS m/z: 532(M⁺), 55(100%).

UV λ_(max) nm: 270, 282, 293.

EXAMPLE 101α,3β-Diacetoxy-20(S)-(3-ethyl-3-hydroxypentylthio)pregna-5,7-diene and1α,3β-diacetoxy-20(R)-(3-ethyl-3-hydroxypentylthio)pregna-5,7-diene

After the procedure of Example 7 was followed using the compoundobtained in Example 6 (180 mg, 0.434 mmol),3-ethyl-3-hydroxypentanethiol (85.7 mg, 0.578 mmol), borontrifluoride-ether complex (71.0 μl, 0.578 mmol), dry dichloromethane (1ml) and triethylsilane (115 μl, 0.723 mmol), the residue was purified bypreparative thin-layer chromatography (4 plates, dichloromethane:ethylacetate=9:1, developed once) to give a mixture of the title compounds asa colorless oil as well as a recovered material (50.1 mg). Thus obtainedmixture was further purified by preparative thin-layer chromatography (4plates, dichloromethane:ethyl acetate=30:1, developed 5 times) to givethe title compounds 20S-isomer (12.5 mg, 5%) and 20R-isomer (28.2 mg,12%) both as colorless oils.

20S-isomer:

IR(neat): 3500, 2950, 1740, 1460, 1370, 1240, 1030 cm⁻¹.

¹ H NMRδ: 5.68-5.60(m,1H), 5.40-5.31(m,1H), 5.07-4.85(m,2H),2.59(t,J=7.8 Hz,2H), 2.09(s,3H), 2.04(s,3H), 1.49(q,J=7.3 Hz,4H),1.40(d,J=6.6 Hz,3H), 1.01(s,3H), 0.87(t,J=7.3 Hz,6H), 0.65(s,3H).

MS m/z: 546(M⁺), 55(100%).

UV λ_(max) nm: 270, 281, 293

20R-isomer:

IR(neat): 3500, 2950, 1740, 1460, 1370, 1240, 1030 cm⁻¹.

¹ H NMRδ: 5.70-5.60(m,1H), 5.41-5.30(m,1H), 5.05-4.84(m,2H),2.56(t,J=8.2 Hz,2H), 2.08(s,3H), 2.03(s,3H), 1.49(q,J=7.3 Hz,4H),1.30(d,J=6.6 Hz,3H), 1.01(s,3H), 0.87(t,J=7.3 Hz,6H), 0.69(s,3H).

MS m/z: 546(M⁺), 55(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 111α,3β-Diacetoxy-20(S)-(5-hydroxy-5-methylhexylthio)pregna-5,7-diene and1α,3β-diacetoxy-20(R)-(5-hydroxy-5-methylhexylthio)pregna-5,7-diene

After the procedure of Example 7 was followed using the compoundobtained in Example 6 (200 mg, 0.482 mmol), the compound obtained inExample 2 (85.7 mg, 0.578 mmol), boron trifluoride-ether complex (71.0μl, 0.578 mmol), dry dichloromethane (1 ml) and triethylsilane (115 μl,0.723 mmol), the residue was purified by preparative thin-layerchromatography (4 plates, dichloromethane:ethyl acetate=10:1, developed3 times) to give the title compounds S-isomer (10.6 mg, 4%) and R-isomer(37.8 mg, 14%) both as colorless oils.

20S-isomer:

IR(neat): 3500, 2950, 1740, 1460, 1370, 1240, 1030 cm⁻¹.

¹ H NMRδ: 5.71-5.63(m,1H), 5.43-5.35(m,1H), 5.07-4.88(m,2H), 2.09(s,3H),2.04(s,3H), 1.38(d,J=6.3 Hz,3H), 1.22(s,6H), 1.01(s,3H), 0.65(s,3H).

MS m/z: 546(M⁺), 278(100%).

UV λ_(max) nm: 270, 281, 293.

20R-isomer:

IR(neat): 3500, 2950, 1740, 1460, 1370, 1240, 1030 cm⁻¹.

¹ H NMRδ: 5.71-5.64(m,1H), 5.43-5.34(m,1H), 5.08-4.88(m,2H), 2.08(s,3H),2.03(s,3H), 1.29(d,J=6.6 Hz,3H), 1.22(s,6H), 1.01(s,3H), 0.69(s,3H).

MS m/z: 546(M⁺), 278(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 121α,3β-Diacetoxy-20(S)-(6-hydroxy-6-methylheptylthio)pregna-5,7-diene and1α,3β-diacetoxy-20(R)-(6-hydroxy-6-methylheptylthio)pregna-5,7-diene

After the procedure of Example 7 was followed using the compoundobtained in Example 6 (200 mg, 0.482 mmol), the compound obtained inExample 3 (93.8 mg, 0.578 mmol), boron trifluoride-ether complex (71.0μl, 0.578 mmol), dry dichloromethane (1 ml) and triethylsilane (115 μl,0.723 mmol), the residue was purified by preparative thin-layerchromatography (4 plates, dichloromethane:ethyl acetate=7:1, developedonce) to give a mixture of the title compounds and the starting thiol asa colorless oil as well as a recovered material (109 mg). Thus obtainedmixture was further purified by preparative thin-layer chromatography (4plates, dichloromethane:ethyl acetate 12:1, developed 5 times) to give amixture of the title compound 20S-isomer and the starting thiol (33.9mg) as well as the title compound 20R-isomer (26.4 mg, 10%) (both ascolorless oils). The former was used in the subsequent reaction in thismixture state.

20R-isomer:

IR(neat): 3500, 2950, 1740, 1460, 1370, 1240, 1030 cm⁻¹.

¹ H NMRδ: 5.71-5.62(m,1H), 5.40-5.32(m,1H), 5.07-4.86(m,2H), 2.08(s,3H),2.03(s,3H), 1.28(d,J=6.8 Hz,3H), 1.21(s,6H), 1.01(s,3H), 0.69(s,3H).

MS m/z: 560(M⁺), 278(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 131α,3β-Diacetoxy-20(S)-(3-hydroxy-3-n-propylhexylthio)pregna-5,7-dieneand1α,3β-diacetoxy-20(R)-(3-hydroxy-3-n-propylhexylthio)pregna-5,7-diene

After the procedure of Example 7 was followed using the compoundobtained in Example 6 (200 mg, 0.482 mmol), the compound obtained inExample 4 (102 mg, 0.578 mmol), boron trifluoride-ether complex (71.0μl, 0.578 mmol), dry dichloromethane (1 ml) and triethylsilane (115 μl,0.723 mmol), the residue was purified by preparative thin-layerchromatography (4 plates, hexane:ethyl acetate:ethanol=4:1:0.1,developed once) to give a mixture of the title compounds as a colorlessoil (134 mg, 48%) as well as a recovered material (48.1 mg). Thusobtained mixture was further purified by preparative thin-layerchromatography (4 plates, dichloromethane:ethyl acetate=30:1, developed4 times) to give the title compounds 20S-isomer (23.6 mg, 9%) and20R-isomer (78.2 mg, 28%) both as colorless oils.

20S-isomer:

IR(neat): 3500, 2950, 1740, 1460, 1370, 1240, 1030 cm⁻¹.

¹ H NMRδ: 5.71-5.61(m,1H), 5.44-5.32(m,1H), 5.08-4.87(m,2H),2.57(t,J=7.8 Hz,2H), 2.09(s,3H), 2.03(s,3H), 1.01(s,3H), 0.92(t,J=6.8Hz,6H), 0.65(s,3H).

MS m/z: 574(M⁺), 157(100%).

UV λ_(max) nm: 270, 281, 293.

20R-isomer:

IR(neat): 3500, 2950, 1740, 1460, 1370, 1240, 1030 cm⁻¹.

¹ H NMRδ: 5.72-5.63(m,1H), 5.44-5.33(m,1H), 5.07-4.90(m,2H),2.54(t,J=7.8 Hz,2H), 2.08(s,3H), 2.03(s,3H), 1.01(s,3H), 0.92(t,J=6.6Hz,6H), 0.69(s,3H).

MS m/z: 574(M⁺), 157(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 141α-Hydroxy-3β-(t-butyldimethylsilyloxy)-20(S)-(4-hydroxy-4-methylpentylthio)pregna-5,7-dieneand1α-hydroxy-3β-(t-butyldimethylsilyloxy)-20(R)-(4-hydroxy-4-methylpentylthio)pregna-5,7-diene

Under an argon atmosphere, to a solution of the compound obtained inExample 9 (mixture) (93.3 mg, 0.175 mmol) in dry tetrahydrofuran (4 ml)was added lithium aluminum hydride (13.3 mg, 0.350 mmol) by portions.The mixture was stirred at room temperature for 30 minutes, thenquenched with a 10% aqueous sodium hydroxide solution and extracted withethyl acetate. The extract was washed with brine and dried overmagnesium sulfate and the solvent was removed under reduced pressure.The residue was purified by preparative thin-layer chromatography (2plates, dichloromethane:ethanol=17:3, developed once) to give 40.1 mg ofcolorless solids. Under an argon atmosphere, the solids were dissolvedinto dimethyl formamide (2.6 ml) and stirred with t-butyldimethylsilylchloride (72.5 mg, 0.481 mmol) and imidazole (65.6 mg, 0.962 mmol) atroom temperature for 2 hours. Then the reaction mixture was poured intowater and extracted with hexane:ethyl acetate=3:1. The organic layer waswashed with brine, dried over magnesium sulfate, and the solvent wasremoved under reduced pressure. The residue was purified by preparativethin-layer chromatography (2 plates, hexane:ethyl acetate=5:1, developed6 times) to give the title compounds 20S-isomer (12.9 mg, 13%) and20R-isomer (23.7 mg, 24%) both as colorless oils.

20S-isomer:

IR(neat): 3450, 2950, 1460, 1380, 1260, 1090 cm⁻¹.

¹ H NMRδ: 5.73-5.64(m,1H), 5.41-5.31(m,1H), 4.11-3.91(m,1H),3.72(brs,1H), 1.40(d,J=6.6 Hz,3H), 1.22(s,6H), 0.94(s,3H), 0.89(s,9H),0.66(s,3H), 0.08(s,6H).

MS m/z: 562(M⁺), 73(100%).

UV λ_(max) nm: 271, 282, 294.

20R-isomer:

IR(neat): 3450, 2950, 1460, 1380, 1260, 1090 cm⁻¹.

¹ H NMRδ: 5.72-5.63(m,1H), 5.38-5.29(m,1H), 4.12-3.92(m,1H),3.72(brs,1H), 1.23(d,J=6.6 Hz,3H), 1.22(s,6H), 0.94(s,3H), 0.88(s,9H),0.71(s,3H), 0.08(s,6H).

MS m/z: 562(M⁺), 73(100%).

UV λ_(max) nm: 271, 282, 294.

EXAMPLE 151α,3β-Dihydroxy-20(S)-(3-hydroxy-3-methylbutylthio)pregna-5,7-diene and1α,3β-dihydroxy-20(R)-(3-hydroxy-3-methylbutylthio)pregna-5,7-diene

Under an argon atmosphere, to a solution of the compound obtained inExample 7 (mixture) (55.0 mg, 0.106 mmol) in dry tetrahydrofuran (2 ml)was added lithium aluminum hydride (8.0 mg, 0.212 mmol) by portions, andthe mixture was stirred at room temperature for 30 minutes. The reactionsolution was quenched with a 10% aqueous sodium hydroxide solution andextracted with ethyl acetate. The organic layer was washed with brine,dried over magnesium sulfate, and the solvent was removed under reducedpressure. The residue was purified by preparative thin-layerchromatography (1 plate, dichloromethane:ethanol=17:1, developed 8times) to give the title compounds 20S-isomer (10.1 mg, 22%) and20R-isomer (19.3 mg, 42%) both as colorless oils.

20S-isomer:

IR(neat): 3400, 2950, 1460, 1380, 1050 cm⁻¹.

¹ H NMRδ: 5.72-5.64(m,1H), 5.39-5.29(m,1H), 4.23-3.92(m,1H),3.76(brs,1H), 2.64(t,J=7.9 Hz,2H), 1.41(d,J=6.6 Hz,3H), 1.25(s,6H),0.95(s,3H), 0.67(s,3H).

MS m/z: 434(M⁺), 69(100%).

UV λ_(max) nm: 272, 282, 293.

20R-isomer:

IR(neat): 3400, 2950, 1460, 1380, 1050 cm⁻¹.

¹ H NMRδ: 5.72-5.63(m,1H), 5.38-5.27(m,1H), 4.15-3.95(m,1H),3.76(brs,1H), 2.62(t,J=8.0 Hz,2H), 1.31(d,J=6.6 Hz,3H), 1.25(s,6H),0.93(s,3H), 0.70(s,3H).

MS m/z: 434(M⁺), 69(100%).

UV λ_(max) nm: 272, 282, 293.

EXAMPLE 161α,3β-Dihydroxy-20(S)-(4-ethyl-4-hydroxyhexylthio)pregna-5,7-diene

After the same reaction as in Example 15 was conducted using the20S-isomer obtained in Example 8 (8.6 mg, 15.3 μmol), drytetrahydrofuran (1.5 ml) and lithium aluminum hydride (1.7 mg, 46.0μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=8:1, developed once) to give the titlecompound as a white solid (5.7 mg, 78%).

IR(neat): 3400, 2950, 1460, 1370, 1050 cm⁻¹.

¹ H NMRδ: 5.77-5.64(m,1H), 5.43-5.34(m,1H), 4.12-4.00(m,1H),3.77(brs,1H), 1.47(q,J=7.3 Hz,4H), 1.40(d,J=6.3 Hz,3H), 0.95(s,3H),0.86(t,J=7.3 Hz,6H), 0.66(s,3H).

MS m/z: 476(M⁺), 143(100%).

UV λ_(max) nm: 271, 282, 294.

EXAMPLE 171α,3β-Dihydroxy-20(R)-(4-ethyl-4-hydroxyhexylthio)pregna-5,7-diene

After the same reaction as in Example 15 was conducted using the20R-isomer obtained in Example 8 (21.1 mg, 37.6 μmol), drytetrahydrofuran (2 ml) and lithium aluminum hydride (4.3 mg, 0.113mmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=8:1, developed once) to give the titlecompound as a white solid (16.0 mg, 89%).

IR(KBr): 3400, 2950, 1460, 1370, 1050 cm⁻¹.

¹ H NMRδ: 5.76-5.68(m,1H), 5.43-5.34(m,1H), 4.15-4.00(m,1H),3.78(brs,1H), 1.47(q,J=7.3 Hz,4H), 1.29(d,J=6.3 Hz,3H), 0.95(s,3H),0.86(t,J=7.3 Hz,6H), 0.71(s,3H).

MS m/z: 476(M⁺), 143(100%).

UV λ_(max) nm: 271, 282, 294.

EXAMPLE 181α,3β-Dihydroxy-20(S)-(4-hydroxy-4-methylpentylthio)pregna-5,7-diene

Under an argon atmosphere, to a solution of the 20S-isomer obtained inExample 14 (12.9 mg, 22.9 μmol) in dry tetrahydrofuran (1.5 ml) wasadded tetra-n-butylammonium fluoride (1M solution in tetrahydrofuran, 1ml), and the mixture was gently refluxed for 16 hours. The reactionmixture was poured into water and extracted with ethyl acetate. Theorganic layer was washed with an aqueous saturated sodium bicarbonatesolution and brine, dried over magnesium sulfate, and the solvent wasremoved under reduced pressure. The residue was purified by preparativethin-layer chromatography (1 plate, dichloromethane:ethanol=9:1,developed once) to give the title compound as a colorless oil (7.7 mg,75%).

IR(neat): 3400, 2950, 1460, 1370, 1050 cm⁻¹.

¹ H NMRδ: 5.72-5.64(m,1H), 5.39-5.29(m,1H), 4.23-3.42(m,1H),3.77(brs,1H), 1.40(d,J=6.6 Hz,3H), 1.23(s,6H), 0.95(s,3H), 0.66(s,3H).

MS m/z: 448(M⁺), 55(100%).

UV λ_(max) nm: 271, 282, 294.

EXAMPLE 191α,3β-Dihydroxy-20(R)-(4-hydroxy-4-methylpentylthio)pregna-5,7-diene

The same reaction as in Example 18 was conducted using the 20R-isomerobtained in Example 14 (23.7 mg, 42.1 μmol), dry tetrahydrofuran (1.5ml) and tetra-n-butylammonium fluoride (1M solution in tetrahydrofuran,1 ml) to give the title compound as a colorless oil (10.0 mg, 53%).

IR(neat): 3400, 2950, 1460, 1370, 1060 cm⁻¹.

¹ H NMRδ: 5.80-5.67(m,1H), 5.41-5.31(m,1H), 4.18-3.96(m,1H),3.78(brs,1H), 1.29(d,J=6.6 Hz,3H), 1.22(s,6H), 0.95(s,3H), 0.71(s,3H).

MS m/z: 448(M⁺), 55(100%).

UV λ_(max) nm: 271, 282, 294.

EXAMPLE 201α,3β-Dihydroxy-20(S)-(3-ethyl-3-hydroxypentylthio)pregna-5,7-diene

After the same synthetic reaction as in Example 15 was conducted usingthe 20S-isomer obtained in Example 10 (12.5 mg, 22.9 μmol), drytetrahydrofuran (1 ml) and lithium aluminum hydride (2.6 mg, 68.7 μmol),the residue was purified by preparative thin-layer chromatography (1plate, dichloromethane:ethanol=9:1, developed once) to give the titlecompound as a colorless oil (8.2 mg, 77%).

IR(neat): 3400, 2950, 1460, 1370, 1030 cm⁻¹.

¹ H NMRδ: 5.76-5.67(m,1H), 5.40-5.30(m,1H), 4.15-3.99(m,1H),3.76(brs,1H), 2.58(t,J=8.0 Hz,2H), 1.50(q,J=7.3 Hz,4H), 1.41(d,J=6.8Hz,3H), 0.95(s,3H), 0.87(t,J=7.3 Hz,6H), 0.67(s,3H).

MS m/z: 462(M⁺), 55(100%).

UV λ_(max) nm: 271, 282, 294.

EXAMPLE 211α,3β-Dihydroxy-20(R)-(3-ethyl-3-hydroxypentylthio)pregna-5,7-diene

After the same reaction as in Example 15 was conducted using the20R-isomer obtained in Example 10 (28.2 mg, 51.6 μmol), drytetrahydrofuran (2 ml) and lithium aluminum hydride (5.9 mg, 0.155mmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=9:1, developed once) to give the titlecompound as a colorless oil (8.2 mg, 77%).

IR(neat): 3400, 2950, 1460, 1370, 1030 cm⁻¹.

¹ H NMRδ: 5.73-5.65(m,1H), 5.38-5.29(m,1H), 4.15-3.95(m,1H),3.77(brs,1H), 2.56(t,J=8.0 Hz,2H), 1.49(q,J=7.3 Hz,4H), 1.31(d,J=6.6Hz,3H), 0.94(s,3H), 0.87(t,J=7.3 Hz,6H), 0.71(s,3H).

MS m/z: 462(M⁺), 55(100%).

UV λ_(max) nm: 271, 282, 294.

EXAMPLE 221α,3β-Dihydroxy-20(S)-(5-hydroxy-5-methylhexylthio)pregna-5,7-diene

After the same reaction as in Example 15 was conducted using the20S-isomer obtained in Example 11 (10.6 mg, 19.4 μmol), drytetrahydrofuran (1 ml) and lithium aluminum hydride (2.5 mg, 65.8 μmol),the residue was purified by preparative thin-layer chromatography (1plate, dichloromethane:ethanol=7:1, developed once) to give the titlecompound as a white solid (6.1 mg, 68%).

IR(neat): 3400, 2950, 1460, 1370, 1050 cm⁻¹.

¹ H NMRδ: 5.79-5.68(m,1H), 5.43-5.35(m,1H), 4.13-3.97(m,1H),3.75(brs,1H), 1.40(d,J=6.6 Hz,3H), 1.22(s,6H), 0.94(s,3H), 0.66(s,3H).

MS m/z: 462(M⁺), 131(100%).

UV λ_(max) nm: 271, 282, 294.

EXAMPLE 231α,3β-Dihydroxy-20(R)-(5-hydroxy-5-methylhexylthio)pregna-5,7-diene

After the same reaction as in Example 15 was conducted using the20R-isomer obtained in Example 11 (36.5 mg, 69.1 μmol), drytetrahydrofuran (2 ml) and lithium aluminum hydride (7.9 mg, 0.207mmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=7:1, developed once) to give the titlecompound as a colorless oil (25.0 mg, 78%).

IR(neat): 3400, 2950, 1460, 1370, 1050 cm⁻¹.

¹ H NMRδ: 5.73-5.65(m,1H), 5.39-5.30(m,1H), 4.14-3.95(m,1H),3.77(brs,1H), 1.29(d,J=6.3 Hz,3H), 1.21(s,6H), 0.94(s,3H), 0.70(s,3H).

MS m/z: 462(M⁺), 131(100%).

UV λ_(max) nm: 271, 282, 294.

EXAMPLE 241α,3β-Dihydroxy-20(S)-(6-hydroxy-6-methylheptylthio)pregna-5,7-diene

After the same reaction as in Example 15 was conducted using the mixtureof the 20S-isomer and the starting thiol obtained in Example 12 (33.9mg), dry tetrahydrofuran (1 ml) and lithium aluminum hydride (20.0 mg,0.527 mmol), the residue was purified by preparative thin-layerchromatography (1 plate, dichloromethane:ethanol=7:1, developed once) togive the title compound as a colorless oil (5.8 mg).

IR(neat): 3400, 2940, 1460, 1370, 1050 cm⁻¹.

¹ H NMRδ: 5.75-5.68(m,1H), 5.42-5.33(m,1H), 4.12-3.97(m,1H),3.75(brs,1H), 1.40(d,J=6.6 Hz,3H), 1.21(s,6H), 0.94(s,3H), 0.66(s,3H).

MS m/z: 476(M⁺), 171(100%).

UV λ_(max) nm: 271, 282, 294.

EXAMPLE 251α,3β-Dihydroxy-20(R)-(6-hydroxy-6-methylheptylthio)pregna-5,7-diene

After the same reaction as in Example 15 was conducted using the20R-isomer obtained in Example 12 (26.4 mg, 47.1 μmol), drytetrahydrofuran (2 ml) and lithium aluminum hydride (5.4 mg, 0.141mmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=7:1, developed once) to give the titlecompound as a colorless oil (15.0 mg, 67%).

IR(neat): 3400, 2940, 1460, 1370, 1050 cm⁻¹.

¹ H NMRδ: 5.75-5.65(m,1H), 5.39-5.30(m,1H), 4.14-3.96(m,1H),3.78(brs,1H), 1.29(d,J=6.3 Hz,3H), 1.21(s,6H), 0.95(s,3H), 0.71(s,3H).

MS m/z: 476(M⁺), 171(100%).

UV λ_(max) nm: 271, 282, 294.

EXAMPLE 261α,3β-Dihydroxy-20(S)-(3-hydroxy-3-n-propylhexylthio)pregna-5,7-diene

After the same reaction as in Example 15 was conducted using the20S-isomer obtained in Example 13 (35.9 mg, 62.4 μmol), drytetrahydrofuran (3 ml) and lithium aluminum hydride (7.1 mg, 0.187mmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=6:1, developed once) to give the titlecompound as a colorless oil (21.4 mg, 70%).

IR(neat): 3400, 2950, 1460, 1370, 1030 cm⁻¹.

¹ H NMRδ: 5.76-5.66(m,1H), 5.42-5.32(m,1H), 4.16-3.96(m,1H),3.76(brs,1H), 2.58(t,J=8.0 Hz,2H), 0.94(s,3H), 0.92(t,J=6.8 Hz,6H),0.66(s,3H).

MS m/z: 490(M⁺), 157(100%).

UV λ_(max) nm: 271, 282, 294.

EXAMPLE 271α,3β-Dihydroxy-20(R)-(3-hydroxy-3-n-propylhexylthio)pregna-5,7-diene

After the same reaction as in Example 15 was conducted using the20R-isomer obtained in Example 13 (126 mg, 0.220 mmol), drytetrahydrofuran (10 ml) and lithium aluminum hydride (25 mg, 0.660mmol), the residue was purified by preparative thin-layer chromatography(2 plates, dichloromethane:ethanol=6:1, developed once) to give thetitle compound as a white solid (74.4 mg, 69%).

IR(neat): 3400, 2950, 1460, 1370, 1050 cm⁻¹.

¹ H NMRδ: 5.75-5.63(m,1H), 5.41-5.29(m,1H), 4.16-3.93(m,1H),3.75(brs,1H), 2.55(t,J=7.8 Hz,2H), 1.00-0.84(s and t,9H), 0.70(s,3H).

MS m/z: 490(M⁺), 157(100%).

UV λ_(max) nm: 271, 282, 294.

EXAMPLE 281α,3β-Dihydroxy-20(S)-(3-hydroxy-3-methylbutylthio)-9,10-secopregna-5,7,10(19)-triene

The 20S-isomer obtained in Example 15 (10.1 mg, 23.2 μmol) was dissolvedinto ethanol (200 ml) and irradiated using a 400 W high-pressure mercurylamp with a Vycor filter for 2 minutes under bubbling with argon at 0°C., and then gently refluxed for 2 hours. The solvent was removed andthe residue was purified by preparative thin-layer chromatography (1plate, dichloromethane:ethanol=10:1, developed 3 times) to give thetitle compound as a colorless oil (1.7 mg, 17%).

IR(neat): 3380, 2920, 1440, 1370, 1050 cm⁻¹.

¹ H NMRδ: 6.37(d,J=11.1 Hz,1H), 6.02(d,J=11.1 Hz,1H), 5.33(s,1H),5.00(s,1H), 4.48-4.35(br,1H), 4.30-4.17(br,1H), 2.63(t,J=7.8 Hz,2H),1.39(d,J=6.6 Hz,3H), 1.25(s,6H), 0.58(s,3H).

MS m/z: 434(M⁺), 69(100%).

UV λ_(max) nm: 263, λ_(min) nm: 227.

EXAMPLE 291α,3β-Dihydroxy-20(R)-(3-hydroxy-3-methylbutylthio)-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 28 (irradiation for 3.75 minutes)was conducted using the 20R-isomer obtained in Example 15 (19.3 mg, 44.4μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=10:1, developed 3 times) to give thetitle compound as a colorless oil (1.6 mg, 8%).

IR(neat): 3390, 2920, 1450, 1380, 1060 cm⁻¹.

¹ H NMRδ: 6.37(d,J=11.1 Hz,1H), 6.01(d,J=11.1 Hz,1H), 5.33(s,1H),5.00(s,1H), 4.48-4.36(br,1H), 4.30-4.13(br,1H), 2.61(t,J=8.3 Hz,2H),1.30(d,J=6.6 Hz,3H), 1.25(s,6H), 0.62(s,3H).

MS m/z: 434(M⁺), 69(100%).

UV λ_(max) nm: 263, λ_(min) nm: 227.

EXAMPLE 301α,3β-Dihydroxy-20(S)-(4-ethyl-4-hydroxyhexylthio)-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 28 (irradiation for 1.5 minutes)was conducted using the compound obtained in Example 16 (5.1 mg, 10.7μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=9:1, developed twice) to give thetitle compound as a colorless oil (1.1 mg, 22%).

IR(neat): 3400, 2950, 1450, 1370, 1050 cm⁻¹.

¹ H NMRδ: 6.37(d,J=11.1 Hz,1H), 6.02(d,J=11.1 Hz,1H), 5.33(s,1H),5.00(s,1H), 4.50-4.38(br,1H), 4.30-4.17(br,1H), 1.47(q,J=7.3 Hz,4H),1.38(d,J=6.3 Hz,3H), 0.86(t,J=7.3 Hz,6H), 0.58(s,3H).

MS m/z: 476(M⁺), 69(100%).

UV λ_(max) nm: 263, λ_(min) nm: 227.

EXAMPLE 311α,3β-Dihydroxy-20(R)-(4-ethyl-4-hydroxyhexylthio)-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 28 (irradiation for 2.5 minutes)was conducted using the compound obtained in Example 17 (16.0 mg, 33.6μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=9:1, developed 3 times, then 1 plate,hexane:ethyl acetate:ethanol=5:5:0.3, developed 3 times) to give thetitle compound as a colorless oil (2.2 mg, 14%).

IR(neat): 3400, 2950, 1460, 1380, 1060 cm⁻¹.

¹ H NMRδ: 6.38(d,J=11.2 Hz,1H), 6.01(d,J=11.2 Hz,1H), 5.33(s,1H),5.00(s,1H), 4.52-4.38(br,1H), 4.29-4.16(br,1H), 1.47(q,J=7.3 Hz,4H),1.28(d,J=6.6 Hz,3H), 0.68(t,J=7.3 Hz,6H), 0.62(s,3H).

MS m/z: 476(M⁺), 69(100%).

UV λ_(max) nm: 263, λ_(min) nm: 227.

EXAMPLE 321α,3β-Dihydroxy-20(S)-(4-hydroxy-4-methylpentylthio)-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 28 (irradiation for 1.75 minutes)was conducted using the compound obtained in Example 18 (7.7 mg, 17.2μmol), the residue was purified by preparative thin-layerchromatog-raphy (1 plate, dichloromethane:ethanol=9:1, developed 3times) to give the title compound as a colorless oil (2.0 mg, 26%).

IR(neat): 3400, 2950, 1450, 1380 cm⁻¹.

¹ H NMRδ: 6.37(d,J=11.2 Hz,1H), 6.02(d,J=11.2 Hz,1H), 5.33(s,1H),5.00(s,1H), 4.48-4.35(br,1H), 4.28-4.16(br,1H), 1.38(d,J=6.3 Hz,3H),1.22(s,6H), 0.58(s,3H).

MS m/z: 448(M⁺), 117(100%).

UV λ_(max) nm: 262, λ_(min) nm: 227.

EXAMPLE 331α,3β-Dihydroxy-20(R)-(4-hydroxy-4-methylpentylthio)-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 28 (irradiation for 1.25 minutes)was conducted using the compound obtained in Example 19 (10.0 mg, 22.3μmol), the residue was purified by preparative thin-layerchromatog-raphy (1 plate, dichloromethane:ethanol=9:1, developed 3times) to give the title compound as a colorless oil (1.9 mg, 19%).

IR(neat): 3400, 2950, 1450, 1380, 1060 cm⁻¹.

¹ H NMRδ: 6.38(d,J=11.2 Hz,1H), 6.01(d,J=11.2 Hz,1H), 5.33(s,1H),5.00(s,1H), 4.48-4.37(br,1H), 4.28-4.16(br,1H), 1.28(d,J=6.6 Hz,3H),1.22(s,6H), 0.62(s,3H).

MS m/z: 448(M⁺), 117(100%).

UV λ_(max) nm: 262, λ_(min) nm: 227.

EXAMPLE 341α,3β-Dihydroxy-20(S)-(3-ethyl-3-hydroxypentylthio)-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 28 (irradiation for 1.5 minutes)was conducted using the compound obtained in Example 20 (8.2 mg, 17.7μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=9:1, developed 3 times) to give thetitle compound as a colorless oil (1.7 mg, 21%).

IR(neat): 3400, 2950, 1460, 1370, 1050 cm⁻¹.

¹ H NMRδ: 6.37(d,J=11.2 Hz,1H), 6.02(d,J=11.2 Hz,1H), 5.33(s,1H),5.00(s,1H), 4.49-4.40(br,1H), 4.29-4.18(br,1H), 2.58(t,J=7.9 Hz,2H),1.49(q,J=7.3 Hz,4H), 1.39(d,J=6.6 Hz,3H), 0.87(t,J=7.3 Hz,6H),0.58(s,3H).

MS m/z: 462(M⁺), 55(100%).

UV λ_(max) nm: 262, λ_(min) nm: 227.

EXAMPLE 351α,3β-Dihydroxy-20(R)-(3-ethyl-3-hydroxypentylthio)-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 28 (irradiation for 3.25 minutes)was conducted using the compound obtained in Example 21 (20.9 mg, 45.2μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=9:1, developed 3 times then 1 platehexane:ethyl acetate:ethanol=5:5:0.3, developed 4 times) to give thetitle compound as a colorless oil (2.3 mg, 11%).

IR(neat): 3400, 2950, 1460, 1370, 1050 cm⁻¹.

¹ H NMRδ: 6.38(d,J=11.2 Hz,1H), 6.01(d,J=11.2 Hz,1H), 5.33(s,1H),5.00(s,1H), 4.48-4.40(br,1H), 4.30-4.15(br,1H), 2.55(t,J=7.9 Hz,2H),1.52(q,J=7.3 Hz,4H), 1.30(d,J=6.6 Hz,3H), 0.87(t,J=7.3 Hz,6H),0.62(s,3H).

MS m/z: 462(M⁺), 55(100%).

UV λ_(max) nm: 263, λ_(min) nm: 227.

EXAMPLE 361α,3β-Dihydroxy-20(S)-(5-hydroxy-5-methylhexylthio)-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 28 (irradiation for 1.75 minutes)was conducted using the compound obtained in Example 22 (6.1 mg, 13.2μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=12:1, developed 3 times) to give thetitle compound as a colorless oil (1.2 mg, 20%).

IR(neat): 3400, 2950, 1460, 1370, 1050 cm⁻¹.

¹ H NMRδ: 6.37(d,J=11.2 Hz,1H), 6.02(d,J=11.2 Hz,1H), 5.33(s,1H),5.00(s,1H), 4.48-4.37(br,1H), 4.29-4.13(br,1H), 1.38(d,J=6.3 Hz,3H),1.22(s,6H), 0.58(s,3H).

MS m/z: 462(M⁺), 131(100%).

UV λ_(max) nm: 262, λ_(min) nm: 227.

EXAMPLE 371α,3β-Dihydroxy-20(R)-(5-hydroxy-5-methylhexylthio)-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 28 (irradiation for 3.5 minutes)was conducted using the compound obtained in Example 23 (25.0 mg, 54.0μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=12:1, developed 4 times then 1 plate,hexane:ethyl acetate:ethanol=5:5:0.1, developed 3 times) to give thetitle compound as a colorless oil (2.3 mg, 9%).

IR(neat): 3400, 2950, 1460, 1380, 1060 cm⁻¹.

¹ H NMRδ: 6.38(d,J=11.2 Hz,1H), 6.01(d,J=11.2 Hz,1H), 5.33(s,1H),5.00(s,1H), 4.50-4.35(br,1H), 4.28-4.16(br,1H), 1.28(d,J=6.8 Hz,3H),1.21(s,6H), 0.62(s,3H).

MS m/z: 462(M⁺), 131(100%).

UV λ_(max) nm: 263, λ_(min) nm: 227.

EXAMPLE 381α,3β-Dihydroxy-20(S)-(6-hydroxy-6-methylheptylthio)-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 28 (irradiation for 1.75 minutes)was conducted using the compound obtained in Example 24 (5.8 mg, 12.2μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=12:1, developed 4 times) to give thetitle compound as a colorless oil (0.99 mg, 17%).

IR(neat): 3400, 2950, 1460, 1370, 1050 cm⁻¹.

¹ H NMRδ: 6.37(d,J=11.2 Hz,1H), 6.02(d,J=11.2 Hz,1H), 5.33(s,1H),5.00(s,1H), 4.48-4.38(br,1H), 4.30-4.15(br,1H), 1.38(d,J=6.6 Hz,3H),1.21(s,6H), 0.58(s,3H).

MS m/z: 476(M⁺), 60(100%).

UV λ_(max) nm: 262, λ_(min) nm: 227.

EXAMPLE 391α,3β-Dihydroxy-20(R)-(6-hydroxy-6-methylheptylthio)-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 28 (irradiation for 2.5 minutes)was conducted using the compound obtained in Example 25 (15.0 mg, 31.5μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=12:1, developed 3 times then 1 plate,hexane:ethyl acetate:ethanol=5:5:0.1, developed 4 times) to give thetitle compound as a colorless oil (2.0 mg, 13%).

IR(neat): 3400, 2950, 1460, 1370, 1050 cm⁻¹.

¹ H NMRδ: 6.38(d,J=11.2 Hz,1H), 6.01(d,J=11.2 Hz,1H), 5.33(s,1H),5.00(s,1H), 4.49-4.38(br,1H), 4.29-4.17(br,1H), 1.28(d,J=6.6 Hz,3H),1.21(s,6H), 0.62(s,3H).

MS m/z: 476(M⁺), 60(100%).

UV λ_(max) nm: 263, 80_(min) nm: 227.

EXAMPLE 401α,3β-Dihydroxy-20(S)-(3-hydroxy-3-n-propylhexylthio)-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 28 (irradiation for 3.5 minutes)was conducted using the compound obtained in Example 26 (20.2 mg, 41.2μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=10:1, developed 3 times then 1 plate,hexane:ethyl acetate:ethanol=6:4:0.5, developed 3 times) to give thetitle compound as a colorless oil (1.8 mg, 9%).

IR(neat): 3400, 2950, 1450, 1370, 1050 cm⁻¹.

¹ H NMRδ: 6.37(d,J=11.1 Hz,1H), 6.03(d,J=11.1 Hz,1H), 5.33(s,1H),5.00(s,1H), 4.52-4.38(br,1H), 4.30-4.18(br,1H), 2.57(t,J=8.0 Hz,2H),0.93(t,J=6.8 Hz,6H), 0.58(s,3H).

MS m/z: 490(M⁺), 157(100%).

UV λ_(max) nm: 263, λ_(min) nm: 227.

EXAMPLE 411α,3β-Dihydroxy-20(R)-(3-hydroxy-3-n-propylhexylthio)-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 28, irradiation for 4.75 minutes)was conducted using the compound obtained in Example 27 (41.3 mg, 84.2μmol), the residue was purified by preparative thin-layer chromatography(2 plates, dichloromethane:ethanol=10:1, developed 3 times then 1 plate,hexane:ethyl acetate:ethanol=6:4:0.5, developed 3 times) to give thetitle compound as a colorless oil (4.6 mg, 11%).

IR(neat): 3400, 2950, 1450, 1380, 1060 cm⁻¹.

¹ H NMRδ: 6.38(d,J=11.2 Hz,1H), 6.01(d,J=11.2 Hz,1H), 5.33(s,1H),5.00(s,1H), 4.48-4.38(br,1H), 4.30-4.16(br,1H), 2.55(t,J=8.0 Hz,2H),0.92(t,J=6.8 Hz,6H), 0.62(s,3H).

MS m/z: 490(M⁺), 157(100%).

UV λ_(max) nm: 263, λ_(min) nm: 227.

EXAMPLE 421α,3β-Bis(t-butyldimethylsilyloxy)-16α-hydroxy-17-oxoandrosta-5,7-diene

Under an argon atmosphere, a solution of potassium t-butoxide (4.13 g,36.8 mmol) in dry tetrahydrofuran (500 ml) was cooled to -78° C., and asolution of 1α,3β-bis(t-butyldimethylsilyloxy)-17-oxoandrosta-5,7-diene(13.0 g, 24.5 mmol) in tetrahydrofuran (40 ml) was added dropwise. Afterthe mixture was stirred at the same temperature for 1 hour, a solutionof 2-(phenylsulfonyl)-3-phenyloxazyldine (9.62 g, 36.8 mmol) intetrahydrofuran (40 ml) was added dropwise and the mixture was furtherstirred at -78° C. for 1.5 hour. The reaction mixture was quenched withan aqueous saturated ammonium chloride solution, poured into water andextracted with ethyl acetate. The organic layer was washed with brineand dried over anhydrous magnesium sulfate. The mixture was concentratedunder reduced pressure and the deposited solids were filtered, then thefiltrate was concentrated again and the residue was purified by columnchromatography on silica gel (hexane:ethyl acetate:chloroform=7:1:2) togive the title compound as a white solid (3.10 g, 23%).

IR(KBr): 3480, 2950, 2850, 1750, 1460, 1380, 1250, 1100 cm⁻¹.

¹ H NMRδ: 0.05(s,6H), 0.07(s,3H), 0.11(s,3H), 0.88(s,9H), 0.89(s,9H),0.90(s,3H), 0.93(s,3H), 3.71(brs,1H), 3.97-4.16(m,1H), 4.42(d,J=8.0Hz,1H), 5.43-5.51(m,1H), 5.56-5.64(m,1H).

MS(20 eV) m/z: 546(M⁺), 355(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 431α,3β-Bis(t-butyldimethylsilyloxy)-16α-hydroxypregna-5,7,17(E)-trieneand1α,3β-bis(t-butyldimethylsilyloxy)-16α-hydroxypregna-5,7,17(Z)-triene

Under an argon atmosphere, the mixture of potassium t-butoxide (1.29 g,11.4 mmol) and ethyltriphenyl phosphonium bromide (4.28 g, 11.4 mmol) intetrahydrofuran (50 ml) was stirred at 60° C. for 1.5 hour and thenreturned to room temperature. A solution of the compound obtained inExample 42 (2.10 g, 3.84 mmol) in tetrahydrofuran (20 ml) was added andthe mixture was further stirred at 60° C. for 1 hour. The reactionmixture was poured into water and extracted with ethyl acetate. Theorganic layer was washed with brine and dried over anhydrous magnesiumsulfate, then the solvent was distilled off under reduced pressure. Theresidue was purified by column chromatography on silica gel(hexane:ethyl acetate=7:1) to give the title compounds E-isomer (375 mg,18%) and Z-isomer (351 mg, 16%) as well as a mixture of the both isomers(142 mg, 6%).

E-isomer

IR(nujol): 3450, 2950, 2850, 1460, 1380, 1250, 1100, 1080 cm⁻¹.

¹ H NMRδ: 0.06(s,3H), 0.07(s,6H), 0.11(s,3H), 0.59(s,3H), 0.89(s,18H),0.91(s,3H), 3.71(brs,1H), 3.84-4.12(m,2H), 5.28-5.39(m,1H),5.47-5.64(m,2H).

MS(20 eV) m/z: 558(M⁺), 369(100%).

UV λ_(max) nm: 270, 281, 293.

Z-isomer

IR(nujol): 3450, 2950, 2850, 1450, 1380, 1255, 1100 cm⁻¹.

¹ H NMRδ: 0.05(s,3H), 0.06(s,6H), 0.11(s,3H), 0.70(s,3H), 0.88(s,18H),0.90(s,3H), 1.80(d,J=8.8 Hz,3H), 3.71(brs,1H), 3.97-4.16(m,1H),4.17-4.27(m,1H), 5.26-5.36(m,1H), 5.52-5.70(m,2H).

MS(20 eV) m/z: 558(M⁺), 369(100%).

UV λ_(max) nm: 270, 282, 293.

EXAMPLE 441α,3β-Bis(t-butyldimethylsilyloxy)-16-oxopregna-5,7,17(E)-triene

Under an argon atmosphere, a solution of trichloromethyl chloroformate(118 μl, 0.68 mmol) in dry dichloromethane (3 ml) was cooled to -78° C.and stirred with dimethyl sulfoxide (186 μl, 2.61 mmol) for 5 minutes,and a solution of the E-isomer from the compounds obtained in Example 43(350 mg, 0.63 mmol) in dry dichloromethane (2 ml) was added dropwise.After the mixed solution was stirred at -78° C. for 15 minutes,triethylamine (435 μl, 3.10 mmol) was added, and the mixture was stirredat -78° C. for 15 minutes and at room temperature for 30 minutes. Thereaction solution was poured into water and extracted withdichloromethane. The organic layer was washed with brine and dried overanhydrous magnesium sulfate, then the solvent was distilled off underreduced pressure. The residue was purified by column chromatography onsilica gel (hexane:ethyl acetate=50:3) to give the title compound as apale yellow solid (147 mg, 42%).

IR(KBr): 2950, 2850, 1730, 1650, 1460, 1380, 1250, 1100 cm⁻¹.

¹ H NMRδ: 0.06(s,3H), 0.07(s,3H), 0.08(s,3H), 0.12(s,3H), 0.87(s,3H),0.89(s,18H), 0.99(s,3H), 1.88(d,J=7.4 Hz,3H), 3.73(brs,1H),3.92-4.10(m,1H), 5.28-5.36(m,1H), 5.54-5.67(m,1H), 6.56(q,J=7.4 Hz,1H).

MS(20 eV) m/z: 556(M⁺), 367(100%).

UV λ_(max) nm: 242, 258, 270, 281, 293.

EXAMPLE 451α,3β-Bis(t-butyldimethylsilyloxy)-16-oxopregna-5,7,17(Z)-triene

The same procedure as in Example 44 was followed using a solution of theZ-isomer from the compounds obtained in Example 43 (347 mg, 0.62 mmol)in dry dichloromethane (2 ml), a solution of trichloromethylchloroformate (118 μl, 0.68 mmol) in dry dichloromethane (3 ml),dimethyl sulfoxide (186 μl, 2.61 mmol) and triethylamine (435 μl, 3.10mmol) to give the title compound as a pale yellow solid (111 mg, 32%).

IR(KBr): 2950, 2850, 1720, 1640, 1460, 1380, 1255, 1080 cm⁻¹.

¹ H NMRδ: 0.05(s,6H), 0.06(s,3H), 0.11(s,3H), 0.85(s,3H), 0.86(s,9H),0.88(s,9H), 0.93(s,3H), 2.16(d,J=7.4 Hz,3H), 3.72(brs,1H),3.93-4.12(m,1H), 5.36-5.47(m,1H), 5.56-5.64(m,1H), 6.17(q,J=7.4 Hz,1H).

MS(20 eV) m/z: 556(M⁺), 367(100%).

UV λ_(max) nm: 242, 258, 270, 281, 293.

EXAMPLE 461α,3β-Bis(t-butyldimethylsilyloxy)-16-oxopregna-5,7,17(E)-triene

The mixture of the E-isomer and Z-isomer from the compounds obtained inExample 43 (a mixture of about 1:1, 1.76 g, 3.15 mmol) was dissolvedinto chloroform (150 ml) and stirred with manganese dioxide (70 g) atroom temperature for 1.5 hour. The reaction solution was filteredthrough Celite and the filtrate was concentrated, then the residue waspurified by column chromatography on silica gel (hexane:ethylacetate:chloroform=84:6:1) to give the title compound as a white solid(879 mg, 50%) and the starting Z-isomer (recovery 560 mg, 32%).

EXAMPLE 471α,3β-Bis(t-butyldimethylsilyloxy)-16-oxopregna-5,7,17(Z)-triene

After the same reaction as in Example 44 was conducted using a solutionof the Z-isomer recovered in Example 46 (533 mg, 0.95 mmol) in drydichloromethane (1.5 ml), a solution of bis(trichloromethyl)carbonate(312 mg, 1.05 mmol) in dry dichloromethane (3 ml), dimethyl sulfoxide(284 μl, 4.00 mmol) and triethylamine (666 μl, 4.78 mmol), the residuewas purified by column chromatography on silica gel (hexane:ethylacetate=14:1) to give the title compound as a pale yellow solid (333 mg,63%).

EXAMPLE 48 4-Phenyl-1,2,4-triazoline-3,5-dione adduct of1α,3β-bis(t-butyldimethylsilyloxy)pregna-5,7,17(E)-triene

A solution of 1α,3β-bis(t-butyldimethylsilyloxy)pregna-5,7,17(E)-triene(1.00 g, 1.84 mmol) in dichloromethane (90 ml) was stirred with asolution of 4-phenyl-1,2,4-triazoline-3,5-dione (330 mg, 1.88 mmol) indichloromethane (10 ml) at room temperature for 30 minutes, then thesolvent was distilled off, and the residue was purified by columnchromatography on silica gel (dichloromethane:ethyl acetate=150:1) togive the title compound as a pale yellow solid (1.02 g, 77%).

¹ H NMRδ: 0.07(s,3H), 0.08(s,3H), 0.10(s,3H), 0.13(s,3H), 0.88(s,9H),0.89(s,9H), 0.93(s,3H), 1.01(s,3H), 1.68(d,J=7.1 Hz,3H),3.25(dd,J=4.0,14.0 Hz,1H), 3.85(t,J=2.7 Hz,1H), 4.79(m,1H), 5.17(q,J=7.1Hz,1H), 6.22(d,J=8.2 Hz,1H), 6.38(d,J=8.2 Hz,1H), 7.19-7.49(m,5H).

UV λ_(max) nm: 206, 258.

EXAMPLE 49 4-Phenyl-1,2,4-triazoline-3,5-dione adduct of1α,3β-bis(t-butyldimethylsilyloxy)-16α-hydroxypregna-5,7,17(E)-triene

The compound obtained in Example 48 (931 mg, 1.3 mmol) was dissolvedinto dichloromethane (40 ml) and stirred with selenium dioxide (5.1 mg,45.5 μmol) and t-butyl hydroperoxide (70%, 422 mg, 4.68 mmol) at roomtemperature for 27 hours. The reaction solution was diluted withdichloromethane, washed with brine, and dried over anhydrous magnesiumsulfate, then the solvent was distilled off. The residue was purified bycolumn chromatography on silica gel (dichloromethane:ethyl acetate=20:1)to give the title compound as a pale yellow solid (885 mg, 92%).

IR(neat): 2950, 2850, 1700, 1460, 1400, 1310, 1260, 1100, 1060 cm⁻¹.

¹ H NMRδ: 0.07(s,3H), 0.09(s,3H), 0.10(s,3H), 0.13(s,3H), 0.88(s,9H),0.89(s,9H), 0.93(s,3H), 1.01(s,3H), 1.77(d,J=7.2 Hz,3H),2.94(dd,J=4.6,11.7 Hz,1H), 3.25(dd,J=4.6,12.3 Hz,1H), 3.85(brs,1H),4.54(brs,1H), 4.78(m,1H), 5.69(q,J=7.2 Hz,1H), 6.24(d,J=8.1 Hz,1H),6.30(d,J=8.1 Hz,1H), 7.22-7.48(m,5H).

MS m/z: 733(M⁺), 73(100%).

UV λ_(max) nm: 210, 258.

EXAMPLE 501α,3β-Bis(t-butyldimethylsilyloxy)-16α-hydroxypregna-5,7,17(E)-triene

The compound obtained in Example 49 (80.0 mg, 109 μmol) was dissolvedinto 1,3-dimethyl-2-imidazolidinone (6 ml) and the mixture was stirredat 140° C. for 16 hours. The mixture was poured into water and extractedwith ethyl acetate. The organic layer was washed with brine and driedover anhydrous magnesium sulfate. The solvent was distilled off and theresidue was purified by preparative thin-layer chromatography (1 plate,hexane:ethyl acetate=4:1, developed once) to give the title compound(39.2 mg, 64%).

EXAMPLE 511α,3β-Bis(t-butyldimethylsilyloxy)-20(S)-(3-hydroxy-3-methylbutylthio)-16-oxopregna-5,7-dieneand1α,3β-bis(t-butyldimethylsilyloxy)-20(R)-(3-hydroxy-3-methylbutylthio)-16-oxopregna-5,7-diene

The compound obtained in Example 44 (140 mg, 251 μmol) was dissolvedinto tetrahydrofuran (4 ml) and stirred with 0.1M sodium tetraborate (4ml) and 3-hydroxy-3-methylbutanethiol (121 μl) at room temperature for12 hours. Then, water was added and the mixture was extracted withchloroform. The organic layer was washed with brine and dried overanhydrous magnesium sulfate. After the solvent was distilled off underreduced pressure, the residue was purified by preparative thin-layerchromatography (3 plates, hexane:ethyl acetate=3:1, developed 3 times)to give the title compounds S-isomer (115 mg, 68%) as a white solid andR-isomer (52.0 mg, 31%) as a colorless oil.

20S-isomer

IR(neat): 3460, 2950, 2850, 1740, 1460, 1380, 1260, 1100 cm⁻¹.

¹ H NMRδ: 0.05(s,3H), 0.06(s,3H), 0.07(s,3H), 0.11(s,3H), 0.87(s,3H),0.88(s,9H), 0.89(s,9H), 0.93(s,3H), 1.24(s,6H), 1.57(d,J=6.6 Hz,3H),2.64(t,J=7.8 Hz,2H), 2.97-3.12(m,1H), 3.73(brs,1H), 3.96-4.12(m,1H),5.24-5.32(m,1H), 5.56-6.03(m,1H).

MS(20 eV) m/z: 676(M⁺), 365(100%).

UV λ_(max) nm: 270, 281, 293.

20R-isomer

IR(neat): 3460, 2950, 2850, 1740, 1460, 1370, 1260, 1100 cm⁻¹.

¹ H NMRδ: 0.05(s,6H), 0.07(s,3H), 0.11(s,3H), 0.86(s,3H), 0.87(s,9H),0.89(s,9H), 0.94(s,3H), 1.23(s,6H), 1.44(d,J=6.3 Hz,3H), 2.60(t,J=8.2Hz,2H), 3.25-3.38(m,1H), 3.70(brs,1H), 3.95-4.10(m,1H), 5.44-5.52(m,1H),5.58-5.65(m,1H).

MS(20 eV) m/z: 676(M⁺), 365(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 521α,3β-Bis(t-butyldimethylsilyloxy)-20(S)-(3-hydroxy-3-methylbutylthio)-16-oxopregna-5,7-dieneand1α,3β-bis(t-butyldimethylsilyloxy)-20(R)-(3-hydroxy-3-methylbutylthio)-16-oxopregna-5,7-diene

After the same reaction as in Example 51 was conducted using thecompound obtained in Example 45 (80.0 mg, 144 μmol), 0.1M sodiumtetraborate (2.3 ml), 3-hydroxy-3-methylbutanethiol (80 μl) andtetrahyrdrofuran (2.3 ml), the residue was purified by preparativethin-layer chromatography (2 plates, hexane:ethyl acetate=3:1, developed3 times) to give the title compounds S-isomer (13.6 mg, 14%) andR-isomer (62.5 mg, 64%).

EXAMPLE 531α,3β-Bis(t-butyldimethylsilyloxy)-20(S)-(4-ethyl-4-hydroxyhexylthio)-16-oxopregna-5,7-dieneand1α,3β-bis(t-butyldimethylsilyloxy)-20(R)-(4-ethyl-4-hydroxyhexylthio)-16-oxopregna-5,7-diene

After the same reaction as in Example 51 was conducted using thecompound obtained in Example 44 (110 mg, 197 μmol), 0.1M sodiumtetraborate (3 ml), 4-ethyl-4-hydroxyhexanethiol (100 μl) andtetrahydrofuran (3 ml), the residue was purified by preparativethin-layer chromatography (2 plates, dichloromethane:ethylacetate:ethanol=15:1:0.1, developed twice then 2 plates;, hexane:ethylacetate=4:1, developed 5 times) to give the title compounds S-isomer(64.2 mg, 45%) and R-isomer (8.1 mg, 6%). After the same reaction as inExample 51 was conducted using the compound obtained in Example 45 (90.0mg, 162 μmol), 0.1M sodium tetraborate (2.5 ml),4-ethyl-4-hydroxyhexanethiol (90 μl) and tetrahydrofuran (2.5 ml), theresidue was purified by preparative thin-layer chromatography (2 plates,dichloromethane:ethyl acetate:ethanol=15:1:0.1, developed twice) to givethe title compounds S-isomer (trace) and R-isomer (49.9 mg, 45%).

20S-isomer:

IR(neat): 3500, 2950, 2850, 1740, 1460, 1370, 1250, 1100, 1010 cm⁻¹.

¹ H NMRδ: 0.06(s,3H), 0.07(s,3H), 0.08(s,3H), 0.12(s,3H),0.80-0.98(m,30H), 1.46(q,J=7.3 Hz,4H), 1.56(d,J=6.6 Hz,3H),2.90-3.08(m,1H), 3.73(brs,1H), 3.93-4.15(m,1H), 5.23-5.32(m,1H),5.54-5.64(m,1H).

MS m/z: 718(M⁺), 73(100%).

UV λ_(max) nm: 270, 281, 293.

20R-isomer:

IR(neat): 3500, 2950, 2860, 1740, 1460, 1380, 1260, 1100, 1010 cm⁻¹.

¹ H NMRδ: 0.06(s,6H), 0.07(s,3H), 0.11(s,3H), 0.76-0.94(m,30H),3.23-3.38(m,1H), 3.71(brs,1H), 3.96-4.13(m,1H), 5.46-5.54(m,1H),5.59-5.66(m,1H).

MS m/z: 718(M⁺), 73(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 541α,3β-Bis(t-butyldimethylsilyloxy)-20(S)-(4-hydroxy-4-methylpentylthio)-16-oxopregna-5,7-dieneand1α,3β-bis(t-butyldimethylsilyloxy)-20(R)-(4-hydroxy-4-methylpentylthio)-16-oxopregna-5,7-diene

After the same reaction as in Example 51 was conducted using thecompound obtained in Example 44 (100 mg, 180 μmol), 0.1M sodiumtetraborate (3 ml), 4-hydroxy-4-methyl-1-pentanethiol (100 μl) andtetrahydrofuran (3 ml), the residue was purified by preparativethin-layer chromatography (2 plates, hexane:ethyl acetate=3:1, developed3 times) to give the title compounds S-isomer (85.8 mg, 69%) andR-isomer (19.7 mg, 16%). After the same reaction as in Example 51 wasconducted using the compound obtained in Example 45 (80.0 mg, 144 μmol),0.1M sodium tetraborate (2.3 ml), 4-hydroxy-4-methyl-1-pentanethiol (100μl) and tetrahydrofuran (2.3 ml), the residue was purified bypreparative thin-layer chromatography (2 plates, hexane:ethylacetate=3:1, developed 3 times) to give the title compounds S-isomer(trace) and R-isomer (91.7 mg, 92%).

20S-isomer:

IR(neat): 3450, 2950, 2850, 1740, 1460, 1380, 1260, 1100 cm⁻¹.

¹ H NMRδ: 0.06(s,3H), 0.07(s,3H), 0.08(s,3H), 0.12(s,3H), 0.87(s,3H),0.89(s,9H), 0.90(s,9H), 0.94(s,3H), 1.22(s,6H), 1.56(d,J=6.6 Hz,3H),2.97-3.05(m,1H), 3.72(brs,1H), 3.95-4.16(m,1H), 5.23-5.34(m,1H),5.56-5.64(m,1H).

MS m/z: 690(M⁺), 73(100%).

UV λ_(max) nm: 270, 281, 293.

20R-isomer:

IR(neat): 3450, 2950, 2850, 1740, 1460, 1380, 1250, 1100 cm⁻¹.

¹ H NMRδ: 0.06(s,6H), 0.07(s,3H), 0.11(s,3H), 0.84(s,3H), 0.88(s,9H),0.89(s,9H), 0.94(s,3H), 1.23(s,6H), 1.42(d,J=6.4 Hz,3H),3.21-3.39(m,1H), 3.71(brs,1H), 3.94-4.14(m,1H), 5.45-5.56(m,1H),5.59-5.67(m,1H).

MS m/z: 690(M⁺), 73(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 551α,3β-Bis(t-butyldimethylsilyloxy)-20(S)-(3-ethyl-3-hydroxypentylthio)-16-oxopregna-5,7-dieneand1α,3β-bis(t-butyldimethylsilyloxy)-20(R)-(3-ethyl-3-hydroxypentylthio)-16-oxopregna-5,7-diene

After the same reaction as in Example 51 was conducted using thecompound obtained in Example 44 (152 mg, 273 μmol), 0.1M sodiumtetraborate (4.2 ml), 3-ethyl-3-hydroxy-1-pentanethiol (140 μl) andtetrahydrofuran (4.2 ml), the residue was purified by preparativethin-layer chromatography (2 plates, hexane:ethyl acetate=3:1, developed3 times then 2 plates, dichloromethane:ethyl acetate:ethanol=15:1:0.1,developed twice) to give the title compounds S-isomer (100 mg, 52%) andR-isomer (17.7 mg, 9%). After the same reaction as in Example 51 wasconducted using the compound obtained in Example 45 (42.1 mg, 75.6μmol), 0.1M sodium tetraborate (1.2 ml),3-ethyl-3-hydroxy-1-pentanethiol (40 μl) and tetrahydrofuran (1.2 ml),the residue was purified by preparative thin-layer chromatography (1plate, hexane:ethyl acetate=4:1, developed 3 times) to give the titlecompounds S-isomer (trace) and R-isomer (34.3 mg, 64%).

20S-isomer:

IR(neat): 3500, 2950, 2850, 1740, 1460, 1380, 1250, 1100, 1010 cm⁻¹.

¹ H NMRδ: 0.06(s,3H), 0.07(s,3H), 0.08(s,3H), 0.12(s,3H),0.80-0.98(m,30H), 1.46(q,J=7.3 Hz,4H), 2.59(t,J=8.3 Hz,2H),2.95-3.09(m,1H), 3.72(brs,1H), 3.94-4.16(m,1H), 5.23-5.34(m,1H),5.56-5.64(m,1H).

MS m/z: 704(M⁺), 73(100%).

UV λ_(max) nm: 270, 281, 293.

20R-isomer:

IR(neat): 3500, 2950, 2850, 1740, 1460, 1370, 1250, 1100, 1010 cm⁻¹.

¹ H NMRδ: 0.06(s,6H), 0.07(s,3H), 0.11(s,3H), 0.76-0.94(m,30H),3.23-3.38(m,1H), 3.71(brs,1H), 3.96-4.13(m,1H), 5.46-5.54(m,1H),5.59-5.65(m,1H).

MS m/z: 704(M⁺), 73(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 561α,3β-Bis(t-butyldimethylsilyloxy)-20(S)-(3-hydroxy-3-methylbutylthio)-16β-hydroxypregna-5,7-dieneand1α,3β-bis(t-butyldimethylsilyloxy)-20(S)-(3-hydroxy-3-methylbutylthio)-16α-hydroxypregna-5,7-diene

The 20S-isomer from the compounds obtained in Example 51 (113 mg, 167μmol) was dissolved into tetrahydrofuran (3.5 ml) and lithium aluminumhydride (10.1 mg, 266 μmol) was added by portions. The mixture wasstirred at room temperature for 30 minutes, then quenched with a 10%aqueous sodium hydroxide solution. Water was added and the mixture wasextracted with ethyl acetate. The organic layer was washed with brineand dried over anhydrous magnesium sulfate. The solvent was distilledoff and the residue was purified by preparative thin-layerchromatography (2 plates, hexane:ethyl acetate=1:1, developed twice) togive the title compounds β-isomer (73.4 mg, 65%) as a white solid andα-isomer (22.0 mg, 19%) as a colorless oil.

16β-isomer:

IR(KBr): 3450, 2950, 2850, 1460, 1370, 1250, 1100 cm⁻¹.

¹ H NMRδ: 0.05(s,6H), 0.06(s,3H), 0.10(s,3H), 0.87(s,9H), 0.88(s,9H),0.91(s,3H), 0.93(s,3H), 1.25(s,6H), 1.48(d,J=6.2 Hz,3H), 2.65(t,J=8.1Hz,2H), 3.11-3.25(m,1H), 3.70(brs,1H), 3.97-4.13(m,1H), 4.38-4.55(m,1H),5.27-5.36(m,1H), 5.47-5.63(m,1H).

MS m/z: 678(M⁺), 73(100%).

UV λ_(max) nm: 271, 282, 294.

16α-isomer:

IR(neat): 3400, 2950, 2850, 1460, 1380, 1250, 1100 cm⁻¹.

¹ H NMRδ: 0.05(s,3H), 0.06(s,6H), 0.10(s,3H), 0.72(s,3H), 0.88(s,21H),1.25(s,6H), 1.48(d,J=6.5 Hz,3H), 2.65(t,J=8.0 Hz,2H), 2.84-3.02(m,1H),3.70(brs,1H), 3.97-4.28(m,2H), 5.25-5.34(m,1H), 5.55-5.63(m,1H).

MS m/z: 678(M⁺), 73(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 571α,3β-Bis(t-butyldimethylsilyloxy)-20(R)-(3-hydroxy-3-methylbutylthio)-16β-hydroxypregna-5,7-dieneand1α,3β-bis(t-butyldimethylsilyloxy)-20(R)-(3-hydroxy-3-methylbutylthio)-16α-hydroxypregna-5,7-diene

After the same reaction as in Example 56 was conducted using the20R-isomer from the compounds obtained in Example 51 (51.7 mg, 76.3μmol), tetrahydrofuran (1.5 ml) and lithium aluminum hydride (4.6 mg,122 μmol), the residue was purified by preparative thin-layerchromatography (1 plate, hexane:ethyl acetate=1:1, developed twice) togive the title compounds β-isomer (13.2 mg, 25%) and α-isomer (10.1 mg,19%) both as colorless oils.

16β-isomer:

IR(neat): 3450, 2950, 2850, 1460, 1380, 1250, 1100 cm⁻¹.

¹ H NMRδ: 0.05(s,3H), 0.06(s,6H), 0.11(s,3H), 0.79(s,3H), 0.88(s,18H),0.92(s,3H), 1.25(s,6H), 1.44(d,J=6.6 Hz,3H), 2.69(t,J=8.1 Hz,2H),3.06-3.19(m,1H), 3.71(brs,1H), 3.81-3.95(m,1H), 3.96-4.11(m,1H),5.31-5.39(m,1H), 5.55-5.63(m,1H).

MS m/z: 678(M⁺), 73(100%).

UV λ_(max) nm: 270, 282, 293.

16α-isomer:

IR(neat): 3450, 2950, 2850, 1460, 1380, 1250, 1100 cm⁻¹.

¹ H NMRδ: 0.05(brs,9H), 0.11(s,3H), 0.84(s,3H), 0.88(s,18H), 0.91(s,3H),1.26(s,6H), 1.46(d,J=6.6 Hz,3H), 2.70(t,J=8.1 Hz,2H), 3.02-3.19(m,1H),3.69(brs,1H), 3.95-4.11(m,1H), 4.39-4.53(m,1H), 5.33-5.42(m,1H),5.56-5.66(m,1H).

MS m/z: 678(M⁺), 73(100%).

UV λ_(max) nm: 270, 282, 293.

EXAMPLE 581α,3β-Bis(t-butyldimethylsilyloxy)-20(S)-(4-ethyl-4-hydroxyhexylthio)-16β-hydroxypregna-5,7-dieneand1α,3β-bis(t-butyldimethylsilyloxy)-20(S)-(4-ethyl-4-hydroxyhexylthio)-16α-hydroxypregna-5,7-diene

After the same reaction as in Example 56 was conducted using the20S-isomer from the compounds obtained in Example 53 (61.0 mg, 84.8μmol), tetrahydrofuran (2.4 ml) and lithium aluminum hydride (5.2 mg,136 μmol), the residue was purified by preparative thin-layerchromatography (1 plate, hexane:ethyl acetate=3:1, developed 3 times) togive the title compounds β-isomer (40.4 mg, 66%) and α-isomer (12.1 mg,20%) both as colorless oils.

16β-isomer:

IR(neat): 3450, 2950, 2850, 1460, 1370, 1250, 1100 cm⁻¹.

¹ H NMRδ: 0.05(s,6H), 0.06(s,3H), 0.10(s,3H), 0.78-0.94(m,30H),3.08-3.22(m,1H), 3.70(brs,1H), 3.97-4.13(m,1H), 4.39-4.52(m,1H),5.26-5.36(m,1H), 5.55-5.66(m,1H).

MS m/z: 720(M⁺), 73(100%).

UV λ_(max) nm: 270, 282, 294.

16α-isomer:

IR(neat): 3440, 2950, 2850, 1460, 1380, 1250, 1100 cm⁻¹.

¹ H NMRδ: 0.05(s,3H), 0.06(s,6H), 0.11(s,3H), 0.71(s,3H),0.78-0.94(m,27H), 2.81-2.98(m,1H), 3.70(brs,1H), 3.97-4.11(m,1H),4.15-4.25(m,1H), 5.25-5.33(m,1H), 5.55-5.61(m,1H).

MS m/z: 720(M⁺), 73(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 591α,3β-Bis(t-butyldimethylsilyloxy)-20(R)-(4-ethyl-4-hydroxyhexylthio)-16β-hydroxypregna-5,7-diene

After the same reaction as in Example 56 was conducted using the20R-isomer from the compounds obtained in Example 53 (49.9 mg, 69.4μmol), tetrahydrofuran (2.0 ml) and lithium aluminum hydride (4.2 mg,111 μmol), the residue was purified by preparative thin-layerchromatography (2 plates, hexane:ethyl acetate=3:1, developed 3 times)to give the title compound as a colorless oil (36.7 mg, 73%).

IR(neat): 3450, 2950, 2850, 1460, 1380, 1250, 1100 cm⁻¹.

¹ H NMRδ: 0.05(s,3H), 0.07(s,6H), 0.11(s,3H), 0.78-0.94(m,30H),3.06-3.18(m,1H), 3.71(brs,1H), 3.81-3.95(m,1H), 3.98-4.13(m,1H),5.31-5.39(m,1H), 5.55-5.63(m,1H).

MS m/z: 720(M⁺), 73(100%).

UV λ_(max) nm: 270, 282, 293.

EXAMPLE 601α,3β-Bis(t-butyldimethylsilyloxy)-20(S)-(4-hydroxy-4-methylpentylthio)-16β-hydroxypregna-5,7-dieneand1α,3β-bis(t-butyldimethylsilyloxy)-20(S)-(4-hydroxy-4-methylpentylthio)-16α-hydroxypregna-5,7-diene

After the same reaction as in Example 56 was onducted using the20S-isomer from the compounds obtained in Example 54 (85.0 mg, 123μmol), tetrahydrofuran (2.5 ml) and lithium aluminum hydride (7.5 mg,197 μmol), the residue was purified by preparative thin-layerchromatography (1 plate, hexane:ethyl acetate=1:1, developed 3 timesthen 1 plate, dichloromethane:ethanol=30:1, developed 5 times) to givethe title compounds β-isomer (58.3 mg, 68%) and α-isomer (9.7 mg, 11%)both as colorless oils.

16β-isomer:

IR(neat): 3400, 2950, 2850, 1460, 1380, 1250, 1100 cm⁻¹.

¹ H NMRδ: 0.05(s,6H), 0.06(s,3H), 0.10(s,3H), 0.87(s,9H), 0.88(s,9H),0.92(s,3H), 0.93(s,3H), 1.25(s,6H), 1.46(d,J=6.3 Hz,3H),3.07-3.22(m,1H), 3.70(brs,1H), 3.97-4.12(m,1H), 4.38-4.51(m,1H),5.25-5.35(m,1H), 5.54-5.66(m,1H).

MS m/z: 692(M⁺), 73(100%).

UV λ_(max) nm: 270, 282, 293.

16α-isomer:

IR(neat): 3420, 2950, 2850, 1460, 1370, 1250, 1090 cm⁻¹.

¹ H NMRδ: 0.05(s,3H), 0.06(s,6H), 0.10(s,3H), 0.72(s,3H), 0.88(s,21H),1.25(s,6H), 1.48(d,J=6.4 Hz,3H), 2.85-3.03(m,1H), 3.71(brs,1H),3.96-4.27(m,2H), 5.25-5.34(m,1H), 5.54-5.64(m,1H).

MS m/z: 692(M⁺), 73(100%).

UV λ_(max) nm: 270, 282, 293.

EXAMPLE 611α,3β-Bis(t-butyldimethylsilyloxy)-20(R)-(4-hydroxy-4-methylpentylthio)-16β-hydroxypregna-5,7-diene

After the same synthetic reaction as in Example 56 was conducted usingthe 20R-isomer from the compounds obtained in Example 54 (91.1 mg, 132μmol), tetrahydrofuran (2.5 ml) and lithium aluminum hydride (8.0 mg,211 μmol), the residue was purified by preparative thin-layerchromatography (2 plates, dichloromethane:ethanol=20:1, developed 5times) to give the title compound as a colorless oil (57.0 mg, 62%).

IR(neat): 3450, 2950, 2850, 1460, 1380, 1250, 1100 cm⁻¹.

¹ H NMRδ: 0.05(s,3H), 0.06(s,6H), 0.11(s,3H), 0.72(s,3H), 0.88(s,18H),0.92(s,3H), 1.26(s,6H), 1.44(d,J=6.6 Hz,3H), 2.69(t,J=8.0 Hz,2H),2.97-3.08(m,1H), 3.71(brs,1H), 3.81-3.94(m,1H), 3.96-4.11(m,1H),5.30-5.39(m,1H), 5.55-5.62(m,1H).

MS m/z: 692(M⁺), 73(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 621α,3β-Bis(t-butyldimethylsilyloxy)-20(S)-(3-ethyl-3-hydroxypentylthio)-16β-hydroxypregna-5,7-dieneand1α,3β-bis(t-butyldimethylsilyloxy)-20(S)-(3-ethyl-3-hydroxypentylthio)-16α-hydroxypregna-5,7-diene

After the same synthetic reaction as in Example 56 was conducted usingthe 20S-isomer from the compounds obtained in Example 55 (98.8 mg, 140μmol), tetrahydrofuran (5.0 ml) and lithium aluminum hydride (8.5 mg,224 μmol), the residue was purified by preparative thin-layerchromatography (2 plates, hexane:ethyl acetate=3:1, developed 3 times)to give the title compounds β-isomer (42.6 mg, 43%) and α-isomer (12.2mg, 12%) both as colorless oils.

16β-isomer:

IR(neat): 3450, 2950, 2850, 1460, 1380, 1260, 1100 cm⁻¹.

¹ H NMRδ: 0.05(s,6H), 0.06(s,3H), 0.10(s,3H), 0.81-0.97(m,30H),2.60(t,J=8.1 Hz,2H), 3.09-3.25(m,1H), 3.69(brs,1H), 3.94-4.14(m,1H),4.38-4.51(m,1H), 5.26-5.35(m,1H), 5.55-5.60(m,1H).

MS m/z: 706(M⁺), 73(100%).

UV λ_(max) nm: 271, 282, 294.

16α-isomer:

IR(neat): 3400, 2950, 2850, 1460, 1370, 1250, 1100 cm⁻¹.

¹ H NMRδ: 0.05(s,3H), 0.06(s,6H), 0.10(s,3H), 0.72(s,3H),0.80-0.94(m,27H), 2.59(t,J=8.1 Hz,2H), 2.84-2.98(m,1H), 3.69(brs,1H),3.95-4.10(m,1H), 4.12-4.19(m,1H), 5.25-5.34(m,1H), 5.55-5.63(m,1H).

MS m/z: 706(M⁺), 73(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 631α,3β-Bis(t-butyldimethylsilyloxy)-20(R)-(3-ethyl-3-hydroxypentylthio)-16β-hydroxypregna-5,7-diene

After the same synthetic reaction as in Example 56 was conducted usingthe 20R-isomer from the compounds obtained in Example 55 (33.3 mg, 47.2μmol), tetrahydrofuran (1.1 ml) and lithium aluminum hydride (2.9 mg,75.2 μmol), the residue was purified by preparative thin-layerchromatography (1 plate, hexane:ethyl acetate=3:1, developed 3 times) togive the title compound as a colorless oil (18.2 mg, 55%).

IR(neat): 3430, 2950, 2850, 1460, 1380, 1250, 1100 cm⁻¹.

¹ H NMRδ: 0.05(s,3H), 0.06(s,6H), 0.11(s,3H), 0.78(s,3H),0.81-0.94(m,27H), 2.64(t,J=8.2 Hz,2H), 3.07-3.19(m,1H), 3.71(brs,1H),3.82-3.94(m,1H), 3.97-4.11(m,1H), 5.31-5.39(m,1H), 5.55-5.63(m,1H).

MS m/z: 706(M⁺), 73(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 6420(S)-(3-Hydroxy-3-methylbutylthio)-1α,3β,16β-trihydroxypregna-5,7-diene

Under an argon atmosphere, the 16β-isomer from the compounds obtained inExample 56 (70.1 mg, 103 μmol) was dissolved into dry tetrahydrofuran(1.1 ml) and tetra-n-butylammonium fluoride (1M solution intetrahydrofuran, 1.1 ml) was added, and the mixture was gently refluxedfor 16 hours. The mixture was poured into water and extracted with ethylacetate. The organic layer was washed successively with 10% hydrochloricacid, an aqueous saturated sodium bicarbonate solution and brine, anddried over anhydrous magnesium sulfate. After the solvent was distilledoff under reduced pressure, the residue was purified by preparativethin-layer chromatography (1 plate, dichloromethane:ethanol=5:1,developed once) to give the title compound as a colorless oil (41.1 mg,89%).

IR(neat): 3400, 2950, 1460, 1420, 1380, 1210, 1150, 1050 cm⁻¹.

¹ H NMRδ: 0.93(s,3H), 0.94(s,3H), 1.24(s,6H), 1.46(d,J=6.3 Hz,3H),2.62(t,J=7.8 Hz,2H), 3.06-3.24(m,1H), 3.73(brs,1H), 3.91-4.10(m,1H),4.33-4.49(m,1H), 5.30-5.40(m,1H), 5.61-5.71(m,1H).

MS m/z: 450(M⁺), 69(100%).

UV λ_(max) nm: 271, 282, 293.

EXAMPLE 6520(S)-(3-Hydroxy-3-methylbutylthio)-1α,3β,16α-trihydroxypregna-5,7-diene

After the same reaction as in Example 64 was conducted using the16α-isomer from the compounds obtained in Example 56 (22.0 mg, 32.4μmol), dry tetrahydrofuran (1.1 ml) and tetra-n-butylammonium fluoride(1M solution in tetrahydrofuran, 1.1 ml), the residue was purified bypreparative thin-layer chromatography (1 plate,dichloromethane:ethanol=5:1, developed once) to give the title compoundas a colorless oil (11.5 mg, 79%).

IR(neat): 3350, 2950, 1450, 1380, 1050 cm⁻¹.

¹ H NMRδ: 0.72(s,3H), 0.93(s,3H), 1.25(s,6H), 1.48(d,J=6.9 Hz,3H),2.65(t,J=8.1 Hz,2H), 2.85-3.00(m,1H), 3.77(brs,1H), 4.00-4.26(m,2H),5.31-5.40(m,1H), 5.68-5.76(m,1H).

MS m/z: 450(M⁺), 69(100%).

UV λ_(max) nm: 270, 282, 293.

EXAMPLE 6620(R)-(3-Hydroxy-3-methylbutylthio)-1α,3β,16β-trihydroxypregna-5,7-diene

After the same reaction as in Example 64 was conducted using the16β-isomer from compounds obtained in Example 57 (55.1 mg, 81.1 μmol),dry tetrahydrofuran (1.0 ml) and tetra-n-butylammonium fluoride (1Msolution tetrahydrofuran, 1.0 ml), the residue was purified bypreparative thin-layer chromatography (1 plate,dichloromethane:ethanol=5:1, developed once) to give the title compoundas a colorless oil (31.9 mg, 88%).

IR(neat): 3400, 2950, 1450, 1380, 1210, 1030 cm⁻¹.

¹ H NMRδ: 0.79(s,3H), 0.95(s,3H), 1.24(s,6H), 1.44(d,=6.9 Hz,3H),2.69(t,J=8.3 Hz,2H), 3.06-3.20(m,1H), 3.76(brs,1H), 3.28-3.95(m,1H),3.98-4.15(m,1H), 5.37-5.45(m,1H), 5.66-5.75(m,1H).

MS m/z: 450(M⁺), 69(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 6720(R)-(3-Hydroxy-3-methylbutylthio)-1α,3β,16α-trihydroxypregna-5,7-diene

After the same reaction as in Example 64 was conducted using the16α-isomer from the compounds obtained in Example 57 (15.8 mg, 23.3μmol), dry tetrahydrofuran (1.0 ml) and tetra-n-butylammonium fluoride(1M solution in tetrahydrofuran, 0.8 ml), the residue was purified bypreparative thin-layer chromatography (1 plate,dichloromethane:ethanol=5:1, developed once) to give the title compoundas a colorless oil (8.6 mg, 82%).

IR(neat): 3400, 2950, 1450, 1380, 1330, 1210, 1030 cm⁻¹.

¹ H NMRδ: 0.85(s,3H), 0.96(s,3H), 1.26(s,6H), 1.46(d,J=6.6 Hz,3H),2.70(t,J=7.9 Hz,2H), 3.04-3.19(m,1H), 3.75(brs,1H), 3.97-4.13(m,1H),4.42-4.53(m,1H), 5.39-5.47(m,1H), 5.71-5.78(m,1H).

MS m/z: 450(M⁺), 69(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 6820(S)-(4-Ethyl-4-hydroxyhexylthio)-1α,3β,16β-trihydroxypregna-5,7-diene

After the same reaction as in Example 64 was conducted using the16β-isomer from the compounds obtained in Example 58 (36.5 mg, 50.6μmol), dry tetrahydrofuran (1.0 ml) and tetra-n-butylammonium fluoride(1M solution in tetrahydrofuran, 1.0 ml), the residue was purified bypreparative thin-layer chromatography (1 plate,dichloromethane:ethanol=16:3, developed once) to give the title compoundas a colorless oil (21.3 mg, 86%).

IR(neat): 3400, 2950, 1460, 1420, 1370, 1250, 1030 cm⁻¹.

¹ H NMRδ: 0.86(t,J=7.3 Hz,6H), 0.93(s,3H), 0.96(s,3H), 3.03-3.23(m,1H),3.77(brs,1H), 3.96-4.15(m,1H), 4.26-4.52(m,1H), 5.31-5.40(m,1H),5.67-5.76(m,1H).

MS m/z: 492(M⁺), 143(100%).

UV λ_(max) nm: 271, 282, 293.

EXAMPLE 6920(S)-(4-Ethyl-4-hydroxyhexylthio)-1α,3β,16α-trihydroxypregna-5,7-diene

After the same reaction as in Example 64 was conducted using the16α-isomer from the compounds obtained in Example 58 (12.0 mg, 16.6μmol), dry tetrahydrofuran (1.0 ml) and tetra-n-butylammonium fluoride(1M solution in tetrahydrofuran, 1.0 ml), the residue was purified bypreparative thin-layer chromatography (1 plate,dichloromethane:ethanol=16:3, developed once) to give the title compoundas a colorless oil (6.3 mg, 77%).

IR(neat): 3400, 2950, 1450, 1380, 1040 cm⁻¹.

¹ H NMRδ: 0.72(s,3H), 0.86(t,J=7.3 Hz,6H), 0.94(s,3H), 2.80-2.98(m,1H),3.77(brs,1H), 3.96-4.28(m,2H), 5.29-5.39(m,1H), 5.67-5.75(m,1H).

MS m/z: 492(M⁺), 143(100%).

UV λ_(max) nm: 271, 282, 293.

EXAMPLE 7020(R)-(4-Ethyl-4-hydroxyhexylthio)-1α,3β,16β-trihydroxypregna-5,7-diene

After the same reaction as in Example 64 was conducted using thecompound obtained in Example 59 (34.0 mg, 47.1 μmol), drytetrahyteofuran (1.0 ml) and tetra-n-butylammonium fluoride (1M solutionin tetrahydrofuran, 1.0 ml), the residue was purified by preparativethin-layer chromatography (1 plate, dichloromethane:ethanol=16:3,developed once) to give the title compound as a colorless oil (12.1 mg,52%).

IR(neat): 3400, 2950, 1460, 1380, 1040 cm⁻¹.

¹ H NMRδ: 0.80(s,3H), 0.86(t,J=7.3 Hz,6H), 0.97(s,3H), 3.06-3.17(m,1H),3.78(brs,1H), 3.80-4.06(m,2H), 5.36-5.45(m,1H), 5.67-5.76(m,1H).

MS m/z: 492(M⁺), 143(100%).

UV λ_(max) nm: 271, 282, 293.

EXAMPLE 7120(S)-(4-Hydroxy-4-methylpentylthio)-1α,3β,16β-trihydroxypregna-5,7-diene

After the same reaction as in Example 64 was conducted using the16β-isomer from the compounds obtained in Example 60 (58.3 mg, 84.1μmol), dry tetrahydrofuran (1.0 ml) and tetra-n-butylammonium fluoride(1M solution in tetrahydrofuran, 1.0 ml), the residue was purified bypreparative thin-layer chromatography (1 plate,dichloromethane:ethanol=5:1, developed once) to give the title compoundas a colorless oil (22.9 mg, 59%).

IR(neat): 3400, 2950, 1450, 1380, 1050 cm⁻¹.

¹ H NMRδ: 0.94(s,3H), 0.97(s,3H), 1.23(s,6H), 1.47(d,J=6.3 Hz,3H),3.07-3.22(m,1H), 3.78(brs,1H), 4.00-4.16(m,1H), 4.40-4.52(m,1H),5.34-5.41(m,1H), 5.69-5.76(m,1H).

MS m/z: 464(M⁺), 117(100%).

UV λ_(max) nm: 270, 282, 293.

EXAMPLE 7220(S)-(4-Hydroxy-4-methylpentylthio)--1α,3β,16α-trihydroxypregna-5,7-diene

After the same reaction as in Example 64 was conducted using the16α-isomer from the compounds obtained in Example 60 (9.7 mg, 14.0μmol), dry tetrahydrofuran (1.0 ml) and tetra-n-butylammonium fluoride(1M solution in tetrahydrofuran, 1.0 ml), the residue was purified bypreparative thin-layer chromatography (1 plate,dichloromethane:ethanol=5:1, developed once) to give the title compoundas a colorless oil (4.6 mg, 71%).

IR(neat): 3400, 2950, 1450, 1380, 1040 cm⁻¹.

¹ H NMRδ: 0.72(s,3H), 0.94(s,3H), 1.22(s,6H), 1.46(d,J=6.6 Hz,3H),2.83-2.98(m,1H), 3.77(brs,1H), 4.00-4.13(m,1H), 4.16-4.24(m,1H),5.32-5.39(m,1H), 5.68-5.75(m,1H).

MS m/z: 464(M⁺), 117(100%).

UV λ_(max) nm: 270, 282, 293.

EXAMPLE 7320(R)-(4-Hydroxy-4-methylpentylthio)-1α,3β,16β-trihydroxypregna-5,7-diene

After the same reaction as in Example 64 was conducted using thecompound obtained in Example 61 (57.0 mg, 82.2 μmol), drytetrahydrofuran (1.0 ml) and tetra-n-butylammonium fluoride (1M solutionin tetrahydrofuran, 1.0 ml), the residue was purified by preparativethin-layer chromatography (1 plate, dichloromethane:ethanol=5:1,developed once) to give the title compound as a colorless oil (30.4 mg,80%).

IR(neat): 3400, 2950, 1450, 1380, 1220, 1040 cm⁻¹.

¹ H NMRδ: 0.80(s,3H), 0.96(s,3H), 1.22(s,6H), 1.42(d,J=6.9 Hz,3H),3.05-3.18(m,1H), 3.77(brs,1H), 3.80-3.96(m,1H), 3.98-4.16(m,1H),5.38-5.47(m,1H), 5.68-5.75(m,1H).

MS m/z: 464(M⁺), 117(100%).

UV λ_(max) nm: 270, 282, 293.

EXAMPLE 7420(S)-(3-Ethyl-3-hydroxypentylthio)-1α,3β,16β-trihydroxypregna-5,7-diene

After the same reaction as in Example 64 was conducted using the16β-isomer from the compounds obtained in Example 62 (42.6 mg, 60.2μmol), dry tetrahydrofuran (1.0 ml) and tetra-n-butylammonium fluoride(1M solution in tetrahydrofuran, 1.2 ml), the residue was purified bypreparative thin-layer chromatography (1 plate,dichloromethane:ethanol=5:1, developed once) to give the title compoundas a colorless oil (23.9 mg, 83%).

IR(neat): 3400, 2950, 1460, 1380, 1330, 1260, 1050 cm⁻¹.

¹ H NMRδ: 0.87(t,J=7.3 Hz,6H), 0.93(s,3H), 0.95(s,3H), 2.59(t,J=8.2Hz,2H), 3.03-3.24(m,1H), 3.75(brs,1H), 3.93-4.13(m,1H), 4.33-4.51(m,1H),5.28-5.40(m,1H), 5.65-5.74(m,1H).

MS m/z: 478(M⁺), 87(100%).

UV λ_(max) nm: 271, 282, 294.

EXAMPLE 7520(S)-(3-Ethyl-3-hydroxypentylthio)-1α,3β,16α-trihydroxypregna-5,7-diene

After the same reaction as in Example 64 was conducted using the16α-isomer from the compounds obtained in Example 62 (12.2 mg, 17.2μmol), dry tetrahydrofuran (1.0 ml) and tetra-n-butylammonium fluoride(1M solution in tetrahydrofuran, 1.0 ml), the residue was purified bypreparative thin-layer chromatography (1 plate,dichloromethane:ethanol=5:1, developed once) to give the title compoundas a colorless oil (6.3 mg, 77%).

IR(neat): 3400, 2950, 1460, 1380, 1330, 1220, 1040 cm⁻¹.

¹ H NMRδ: 0.72(s,3H), 0.87(t,J=7.3 Hz,6H), 0.93(s,3H), 2.59(t,J=7.9Hz,2H), 2.84-2.99(m,1H), 3.77(brs,1H), 3.96-4.24(m,2H), 5.31-5.40(m,1H),5.67-5.76(m,1H).

MS m/z: 478(M⁺), 87(100%).

UV λ_(max) nm: 271, 282, 293.

EXAMPLE 7620(R)-(3-Ethyl-3-hydroxypentylthio)-1α,3β,16β-trihydroxypregna-5,7-diene

After the same reaction as in Example 64 was conducted using thecompound obtained in Example 63 (18.0 mg, 25.5 μmol), drytetrahydrofuran (1.0 ml) and tetra-n-butylammonium fluoride (1M solutionin tetrahydrofuran, 1.0 ml), the residue was purified by preparativethin-layer chromatography (1 plate, dichloromethane:ethanol=5:1,developed once) to give the title compound as a colorless oil (8.5 mg,70%).

IR(neat): 3400, 2950, 1460, 1380, 1280, 1030 cm⁻¹.

¹ H NMRδ: 0.80(s,3H), 0.87(t,J=7.3 Hz,6H), 0.97(s,3H), 2.64(t,J=8.3Hz,2H), 3.07-3.18(m,1H), 3.78(brs,1H), 3.83-3.96(m,1H), 3.99-4.15(m,1H),5.40-5.48(m,1H), 5.69-5.77(m,1H).

MS m/z: 478(M⁺), 87(100%).

UV λ_(max) nm: 270, 281, 293.

EXAMPLE 7720(S)-(3-Hydroxy-3-methylbutylthio)-1α,3β,16β-trihydroxy-9,10-secopregna-5,7,10(19)-triene

The compound obtained in Example 64 (40.2 mg, 89.2 μmol) was dissolvedinto ethanol (200 ml) and irradiated using a 400 W high-pressure mercurylamp with a Vycor filter for 2.5 minutes under bubbling with argon at 0°C., and then gently refluxed for 2 hours. The solvent was distilled offand the residue was purified by preparative thin-layer chromatography (1plate, dichloromethane:ethanol=5:1, developed 3 times) to give the titlecompound as a colorless oil (4.6 mg, 11%).

IR(neat): 3400, 2950, 1450, 1370, 1200, 1050 cm⁻¹.

¹ H NMRδ: 0.84(s,3H), 1.25(s,6H), 1.47(d,J=6.3 Hz,3H), 2.64(t,J=7.9Hz,2H), 3.05-3.24(m,1H), 4.16-4.29(br,1H), 4.34-4.49(br,2H), 5.00(s,1H),5.33(s,1H), 6.02(d,J=11.6 Hz,1H), 6.36(d,J=11.6 Hz,1H).

MS m/z: 450(M⁺), 69(100%).

UV λ_(max) nm: 263, λ_(min) nm: 227.

EXAMPLE 7820(S)-(3-Hydroxy-3-methylbutylthio)-1α,3β,16α-trihydroxy-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 77 (irradiation for 2.5 minutes)was conducted using the compound obtained in Example 65 (11.5 mg, 25.5μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=6:1, developed 5 times) to give thetitle compound as a colorless oil (0.7 mg, 6%).

IR(neat): 3350, 2950, 1450, 1380, 1200, 1050 cm⁻¹.

¹ H NMRδ: 0.64(s,3H), 1.25(s,6H), 1.46(d,J=6.9 Hz,3H), 2.64(t,J=7.9Hz,2H), 2.82-2.97(m,1H), 4.10-4.30(br,2H), 4.40-4.51(br,1H), 4.99(s,1H),5.33(s,1H), 5.96(d,J=11.1 Hz,1H), 6.37(d,J=11.1 Hz,1H).

MS m/z: 450(M⁺), 69(100%).

UV λ_(max) nm: 263, λ_(min) nm: 227.

EXAMPLE 7920(R)-(3-Hydroxy-3-methylbutylthio)-1α,3β,16β-trihydroxy-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 77 (irradiation for 2.5 minutes)was conducted using the compound obtained in Example 66 (31.9 mg, 70.8μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=6:1, developed twice) to give thetitle compound as a colorless oil (3.5 mg, 11%).

IR(neat): 3350, 2950, 1450, 1380, 1210, 1060 cm⁻¹.

¹ H NMRδ: 0.71(s,3H), 1.25(s,6H), 1.44(d,J=6.6 Hz,3H), 2.70(t,J=7.9Hz,2H), 3.04-3.20(m,1H), 3.84-3.97(br,1H), 4.16-4.35(br,1H),4.37-4.50(br,1H), 5.00(s,1H), 5.34(s,1H), 5.97(d,J=11.7 Hz,1H),6.36(d,J=11.7 Hz,1H).

MS m/z: 450(M⁺), 69(100%).

UV λ_(max) nm: 263, λ_(min) nm: 227.

EXAMPLE 8020(R)-(3-Hydroxy-3-methylbutylthio)-1α,3β,16α-trihydroxy-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 77 (irradiation for 2.0 minutes)was conducted using the compound obtained in Example 67 (8.6 mg, 19.1μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=6:1, developed 5 times) to give thetitle compound as a colorless oil (1.3 mg, 15%).

IR(neat): 3400, 2950, 1460, 1380, 1200, 1060 cm⁻¹.

¹ H NMRδ: 0.76(s,3H), 1.26(s,6H), 1.44(d,J=6.6 Hz,3H), 2.70(t,J=8.1Hz,2H), 3.00-3.16(m,1H), 4.18-4.31(br,1H), 4.37-4.51(br,2H), 5.00(s,1H),5.31(s,1H), 6.07(d,J=11.2 Hz,1H), 6.36(d,J=11.2 Hz,1H).

MS m/z: 450(M⁺), 69(100%).

UV λ_(max) nm: 262, λ_(min) nm: 227.

EXAMPLE 8120(S)-(4-Ethyl-4-hydroxyhexylthio)-1α,3β,16β-trihydroxy-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 77 (irradiation for 2.5 minutes)was conducted using the compound obtained in Example 68 (21.3 mg, 43.2μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=10:1, developed 3 times) to give thetitle compound as a colorless oil (3.9 mg, 18%).

IR(neat): 3400, 2930, 1450, 1380, 1050 cm⁻¹.

¹ H NMRδ: 0.67-0.90(m,9H), 3.03-3.19(m,1H), 4.16-4.28(br,1H),4.34-4.50(br,2H), 5.01(s,1H), 5.33(s,1H), 6.02(d,J=11.2 Hz,1H),6.37(d,J=11.2 Hz,1H).

MS m/z: 492(M⁺), 69(100%).

UV λ_(max) nm: 262, λ_(min) nm: 227.

EXAMPLE 8220(S)-(4-Ethyl-4-hydroxyhexylthio)-1α,3β,16α-trihydroxy-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 77 (irradiation for 1.75 minutes)was conducted using the compound obtained in Example 69 (6.3 mg, 12.7μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=10:1, developed 5 times) to give thetitle compound as a colorless oil (1.3 mg, 21%).

IR(neat): 3400, 2930, 1460, 1380, 1050 cm⁻¹.

¹ H NMRδ: 0.64(s,3H), 0.86(t,J=7.3 Hz,6H), 2.79-2.96(m,1H),4.07-4.30(m,2H), 4.39-4.50(br,1H), 4.99(s,1H), 5.33(s,1H), 5.96(d,J=11.2Hz,1H), 6.37(d,J=11.2 Hz,1H).

MS m/z: 492(M⁺), 69(100%).

UV λ_(max) nm: 262, λ_(min) nm: 227.

EXAMPLE 8320(R)-(4-Ethyl-4-hydroxyhexylthio)-1α,3β,16β-trihydroxy-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 77 (irradiation for 1.75 minutes)was conducted using the compound obtained in Example 70 (12.1 mg, 24.6μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=10:1, developed 3 times) to give thetitle compound as a colorless oil (1.5 mg, 12%).

IR(neat): 3400, 2930, 1460, 1380, 1050 cm⁻¹.

¹ H NMRδ: 0.72(s,3H), 0.86(t,J=7.3 Hz,6H), 3.04-3.20(m,1H),3.81-3.97(m,1H), 4.26-4.31(br,1H), 4.38-4.50(br,1H), 5.01(s,1H),5.35(s,1H), 5.97(d,J=11.2 Hz,1H), 6.36(d,J=11.2 Hz,1H).

MS m/z: 492(M⁺), 69(100%).

UV λ_(max) nm: 262, λ_(min) nm: 227.

EXAMPLE 8420(S)-(4-Hydroxy-4-methylpentylthio)-1α,3β,16β-trihydroxy-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 77 (irradiation for 2.5 minutes)was conducted using the compound obtained in Example 71 (22.9 mg, 49.2μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=10:1, developed 7 times) to give thetitle compound as a colorless oil (2.4 mg, 10%).

IR(neat): 3400, 2930, 1450, 1370, 1200, 1050 cm⁻¹.

¹ H NMRδ: 0.84(s,3H), 1.22(s,6H), 1.46(d,J=6.1 Hz,3H), 3.00-3.20(m,1H),4.16-4.29(br,1H), 4.34-4.50(br,2H), 5.01(s,1H), 5.33(s,1H),6.01(d,J=11.2 Hz,1H), 6.37(d,J=11.2 Hz,1H).

MS m/z: 464(M⁺), 117(100%).

UV λ_(max) nm: 263, λ_(min) nm: 227.

EXAMPLE 8520(S)-(4-Hydroxy-4-methylpentylthio)--1α,3β,16α-trihydroxy-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 77 (irradiation for 1.25 minutes)was conducted using the compound obtained in Example 72 (5.9 mg, 12.7μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=10:1, developed 5 times) to give thetitle compound as a colorless oil (0.5 mg, 8%).

IR(neat): 3350, 2920, 1450, 1370, 1260, 1050 cm⁻¹.

¹ H NMRδ: 0.64(s,3H), 1.22(s,6H), 1.45(d,J=6.6 Hz,3H), 2.79-2.92(m,1H),4.40-4.34(br,2H), 4.37-4.50(br,1H), 4.99(s,1H), 5.33(s,1H),5.95(d,J=11.2 Hz,1H), 6.35(d,J=11.2 Hz,1H).

MS m/z: 464(M⁺), 117(100%).

UV λ_(max) nm: 262, λ_(min) nm: 227.

EXAMPLE 8620(R)-(4-Hydroxy-4-methylpentylthio)-1α,3β,16β-trihydroxy-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 77 (irradiation for 2.25 minutes)was conducted using the compound obtained in Example 73 (18.3 mg, 39.4μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=10:1, developed 5 times) to give thetitle compound as a colorless oil (1.5 mg, 8%).

IR(neat): 3400, 2920, 1450, 1380, 1260, 1050 cm⁻¹.

¹ H NMRδ: 0.72(s,3H), 1.22(s,6H), 1.42(d,J=6.9 Hz,3H), 3.04-3.17(m,1H),3.84-3.97(m,1H), 4.19-4.31(br,1H), 4.38-4.50(br,1H), 5.01(s,1H),5.34(s,1H), 6.00(d,J=11.2 Hz,1H), 6.37(d,J=11.2 Hz,1H).

MS m/z: 464(M⁺), 117(100%).

UV λ_(max) nm: 262, λ_(min) nm: 227.

EXAMPLE 8720(S)-(3-Ethyl-3-hydroxypentylthio)-1α,3β,16β-trihydroxy-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 77 (irradiation for 2.5 minutes)was conducted using the compound obtained in Example 74 (23.9 mg, 49.9μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=10:1, developed 6 times) to give thetitle compound as a colorless oil (4.3 mg, 18%).

IR(neat): 3400, 2930, 1450, 1380, 1050 cm⁻¹.

¹ H NMRδ: 0.84(s,3H), 0.87(t,J=7.3 Hz,6H), 2.59(t,J=8.3 Hz,2H),3.06-3.22(m,1H), 4.18-4.31(br,1H), 4.34-4.50(br,2H), 5.01(s,1H),5.33(s,1H), 6.02(d,J=11.2 Hz,1H), 6.37(d,J=11.2 Hz,1H).

MS m/z: 478(M⁺), 131(100%).

UV λ_(max) nm: 263, λ_(min) nm: 227.

EXAMPLE 8820(S)-(3-Ethyl-3-hydroxypentylthio)-1α,3β,16α-trihydroxy-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 77 (irradiation for 1.5 minutes)was conducted using the compound obtained in Example 75 (6.3 mg, 13.2μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=10:1, developed 8 times) to give thetitle compound as a colorless oil (1.0 mg, 18%).

IR(neat): 3400, 2950, 1450, 1380, 1050 cm⁻¹.

¹ H NMRδ: 0.64(s,3H), 0.87(t,J=7.3 Hz,6H), 2.59(t,J=7.9 Hz,2H),2.83-2.98(m,1H), 4.07-4.31(m,2H), 4.39-4.49(br,1H), 4.99(s,1H),5.34(s,1H), 5.96(d,J=11.2 Hz,1H), 6.37(d,J=11.2 Hz,1H).

MS m/z: 478(M⁺), 131(100%).

UV λ_(max) nm: 263, λ_(min) nm: 227.

EXAMPLE 8920(R)-(3-Ethyl-3-hydroxypentylthio)-1α,3β,16β-trihydroxy-9,10-secopregna-5,7,10(19)-triene

After the same reaction as in Example 77 (irradiation for 1.75 minutes)was conducted using the compound obtained in Example 76 (8.5 mg, 17.8μmol), the residue was purified by preparative thin-layer chromatography(1 plate, dichloromethane:ethanol=10:1, developed 8 times) to give thetitle compound as a colorless oil (1.1 mg, 13%).

IR(neat): 3400, 2920, 1450, 1380, 1140, 1050 cm⁻¹.

¹ H NMRδ: 0.71(s,3H), 0.87(t,J=7.3 Hz,6H), 2.65(t,J=8.2 Hz,2H),3.08-3.17(m,1H), 3.84-3.97(m,1H), 4.18-4.31(m,1H), 4.40-4.50(br,1H),5.01(s,1H), 5.34(s,1H), 5.98(d,J=11.2 Hz,1H), 6.36(d,J=11.2 Hz,1H).

MS m/z: 478(M⁺), 131(100%).

UV λ_(max) nm: 262, λ_(min) nm: 227.

Test Example 1 Experiment on Inhibition of Proliferation of HumanKeratinocytes

1) Human keratinocytes were plated at 2.4×10³ cells/well (0.32 cm²) ontoa 96-well plate on which J2 cells treated with X-rays had previouslybeen plated, and then the plate was incubated with the test compound ateach concentration on KGM/DMEM (1:1) medium for 3 days at 37° C. in 5%CO₂, 95% air.

2) ³ H! Thymidine was added at a final concentration of 1 μCi/ml and theplate was incubated for further 3 days.

3) After the plate was washed with PBS twice, cells were stripped offwith 0.25% trypsin and the amount of ³ H! thymidine taken into DNA wasmeasured by Betaplate (Pharmacia). The uptake rate at each concentrationof the test compound is plotted against 100% corresponding to the ³ H!thymidine uptake in the absence of the test compound. FIGS. 1 and 2 showthe results of 1α,25-dihydroxyvitamin D₃ and the compound obtained inExample 88, respectively.

Test Example 2

1) Human keratinocytes were plated at 2.2×10³ cells/well (0.32 cm²) ontoa 96-well plate, and then the plate was incubated with the test compoundat each concentration on KGM/DMEM (1:1) medium for one day at 37° C. in5% CO₂, 95% air.

2) ³ H! Thymidine was added at a final concentration of 1 μCi/ml and theplate was incubated for further 3 days.

3) After the plate was washed with PBS twice, cells were stripped offwith 0.25% trypsin and the amount of ³ H! thymidine taken into DNA wasmeasured by Betaplate (Pharmacia). The uptake rate at each concentrationof the test compound is plotted against 100% corresponding to the ³ H!thymidine uptake in the absence of the test compound. FIGS. 3, 4 and 5show the results of 1α,25-dihydroxyvitamin D₃, the compound obtained inExample 33 and the compound obtained in Example 35, respectively.

In the graphs of FIGS. 1 to 5, ★, ★★ and ★★★ mean significantdifferences at probabilities of 5%, 1% and 0.1%, respectively. Asevident from FIGS. 1 to 5, the compounds of this invention have a stronginhibitory effect against proliferation of human keratinocytes.

INDUSTRIAL APPLICABILITY

The compounds of this invention, vitamin D₃ derivatives substituted bysulfur atoms at the 22-position have a strong inhibitory effect againstproliferation of keratinocytes.

We claim:
 1. A compound of the general formula (I): ##STR21## wherein R₁represents a C1-10 alkyl group which may be substituted by one or morehydroxyl groups provided that the terminal carbon atom of R₁ group is aprimary carbon atom or a secondary carbon atom, or R₁ is anunsubstituted alkyl group or an alkyl group substituted by 2 or morehydroxyl groups, R₂ represents a hydrogen atom or a hydroxyl group, andR₃ represents a hydrogen atom or a hydroxyl group.
 2. A compoundaccording to claim 1 wherein R₃ is a hydroxyl group.
 3. A compoundaccording to claim 2 wherein R₁ is a C1-10 alkyl group substituted bytwo or more hydroxyl groups.
 4. A compound according to claim 1 of thegeneral formula (II): ##STR22## wherein R₁ represents a C1-10 alkylgroup which may be substituted by one or more hydroxyl groups providedthat the terminal carbon atom of R₁ group is a primary carbon atom or asecondary carbon atom, or R₁ is an unsubstituted alkyl group or an alkylgroup substituted by 2 or more hydroxyl groups, and R₂ represents ahydrogen atom or a hydroxyl group.
 5. A compound according to claim 4wherein R₁ is a C1-10 alkyl group substituted by two or more hydroxylgroups.
 6. A compound according to claim 5 wherein R₁ is a group of thegeneral formula (III): ##STR23## wherein R₄ and R₅, which may be thesame or different, each represents a hydrogen atom or a hydroxyl groupprovided that the both are not hydroxyl groups, m represents an integerof 1 through 4, and n represents an integer of 0 through
 2. 7. Acompound according to claim 1 wherein R₂ is a hydrogen atom.
 8. Acompound according to claim 6 wherein R₂ is a hydrogen atom.
 9. Acompound according to claim 6 wherein the 20-position is inR-configuration.
 10. A compound according to claim 6 wherein the20-position is in S-configuration.
 11. A compound of the general formula(I): ##STR24## wherein R₁ represents a C1-10 alkyl group which may besubstituted by one or more hydroxyl groups, R₂ represents a hydroxylgroup, and R₃ represents a hydrogen atom or a hydroxyl group.
 12. Acompound according to claim 11 wherein R₃ is a hydroxyl group.
 13. Acompound according to claim 11 wherein R₁ is a C₁₋₁₀ alkyl groupsubstituted by one or more hydroxyl groups.
 14. A compound according toclaim 11 of the general formula (II): ##STR25## wherein R₁ represents aC₁₋₁₀ alkyl group which may be substituted by one or more hydroxylgroups, and R₂ represents a hydrogen atom or a hydroxyl group.
 15. Acompound according to claim 11 wherein R₁ is a C₁₋₁₀ alkyl groupsubstituted by one or more hydroxyl groups.
 16. A compound according toclaim 11 wherein the 20-position is in R-configuration.
 17. A compoundaccording to claim 11 wherein the 20-position is in S-configuration. 18.A compound according to claim 11 wherein R₁ is a group of the generalformula (III): ##STR26## wherein R₄ and R₅, which may be the same ordifferent, each represents a hydrogen atom or a hydroxyl group providedthat the both are not hydroxyl groups, m represents an integer of 1through 4, and n represents an integer of 0 through
 2. 19. A compoundaccording to claim 18 wherein the 20-position is in R-configuration. 20.A compound according to claim 18 wherein the 20-position is inS-configuration.
 21. A compound according to claim 18 wherein the R₄ andR₅ are hydrogen atoms.
 22. A compound of the formula (I): ##STR27##wherein R₂ represents a hydrogen atom or a hydroxyl group, R₃ representsa hydrogen atom or a hydroxyl group, and R₁ is a straight chain C₁₋₁₀alkyl group which may be substituted by one or more hydroxyl groups, abranched chain C₁₋₁₀ alkyl group which may be substituted by two or morehydroxyl groups, or a group of the formula (III): ##STR28## wherein R₄represents a hydroxyl group and R₅ represents a hydrogen atom, mrepresents an integer of 1 through 4, and n represents an integer of 0through
 2. 23. A compound of the formula (I): ##STR29## wherein R₂represents a hydrogen atom or a hydroxyl group, R₃ represents a hydrogenatom or a hydroxyl group, and R₁ is selected from the group consistingof 3-hydroxy-3-methylbutyl, 2-hydroxy-3-methylbutyl,4-hydroxy-3-methylbutyl, 2,3-dihydroxy-3-methylbutyl,2,4-dihydroxy-3-methylbutyl, 3,4-dihydroxy-3-methylbutyl,3-hydroxy-3-ethylpentyl, 2-hydroxy-3-ethylpentyl,4-hydroxy-3-ethylpentyl, 2,3-dihydroxy-3-ethylpentyl,2,4-dihydroxy-3-ethylpentyl, 3,4-dihydroxy-3-ethylpentyl,4-hydroxy-4-methylpentyl, 3-hydroxy-4-methylpentyl,5-hydroxy-4-methylpentyl, 3,4-dihydroxy-4-methylpentyl,3,5-dihydroxy-4-methylpentyl, 4,5-dihydroxy-4-methylpentyl,3-hydroxy-3-(n-propyl)hexyl, 4-hydroxy-3-(n-propyl)hexyl,2-hydroxy-3-(n-propyl)hexyl, 2,3-dihydroxy-3-(n-propyl)hexyl,3,4-dihydroxy-3-(n-propyl)hexyl, 2,4-dihydroxy-3-(n-propyl)hexyl,3-hydroxy-4-ethylhexyl, 4-hydroxy-4-ethylhexyl, 5-hydroxy-4-ethylhexyl,3,4-dihydroxy-4-ethylhexyl, 3,5-dihydroxy-4-ethylhexyl,4,5-dihydroxy-4-ethylhexyl, 4-hydroxy-5-methylhexyl,5-hydroxy-5-methylhexyl, 6-hydroxy-5-methylhexyl,4,5-dihydroxy-5-methylhexyl, 4,6-dihydroxy-5-methylhexyl,5,6-dihydroxy-5-methylhexyl, 5-hydroxy-6-methylheptyl,6-hydroxy-6-methylheptyl, 7-hydroxy-6-methylheptyl,5,6-dihydroxy-6-methylheptyl, 5,7-dihydroxy-6-methylheptyl,6,7-dihydroxy-6-methylheptyl, 4-hydroxy-5-ethylheptyl,5-hydroxy-5-ethylheptyl, 6-hydroxy-5-ethylheptyl,4,5-dihydroxy-5-ethylheptyl, 4,6-dihydroxy-5-ethylheptyl,5,6-dihydroxy-5-ethylheptyl, 3-hydroxy-4-(n-propyl)heptyl,4-hydroxy-4-(n-propyl)heptyl, 5-hydroxy-4-(n-propyl)heptyl,3,4-dihydroxy-4-(n-propyl)heptyl, 3,5-dihydroxy-4-(n-propyl)heptyl and4,5-dihydroxy-4-(n-propyl)heptyl groups, preferably3-hydroxy-3-methylbutyl, 2,3-dihydroxy-3-methylbutyl,3,4-dihydroxy-3-methylbutyl, 3-hydroxy-3-ethylpentyl,2,3-dihydroxy-3-ethylpentyl, 3,4-dihydroxy-3-ethylpentyl,4-hydroxy-4-methylpentyl, 3,4-dihydroxy-4-methylpentyl and4,5-dihydroxy-4-methylpentyl.
 24. A compound according to claim 23wherein R₁ is selected from the group consisting of3-hydroxy-3-methylbutyl, 3-hydroxy-3-ethylpentyl and4-hydroxy-4-methylpentyl.
 25. A compound selected from the groupconsisting of1α,3β-Dihydroxy-20(R)-(4-hydroxy-4-methylpentylthio)-9,10-secopregna-5,7,10(19)-triene;1α,3β-Dihydroxy-20(R)-(3-ethyl-3-hydroxypentylthio)-9,10-secopregna-5,7,10(19)-triene;and 20(S)-(3-Ethyl-3-hydroxypentylthio)-1α,3β,16α-trihydroxy-9,10-secopregna-5,7,10(19)-triene.
 26. A compound ofthe general formula (VI): ##STR30## wherein R₆ and R₇, which may be thesame or different, each represents a hydrogen atom or a protectivegroup, and R₈ represents a C1-10 alkyl group which may be substituted.27. A compound according to claim 26 wherein the protective group is anacyl or a substituted silyl group, and R₈ is a C1-10 alkyl groupsubstituted by one or more hydroxyl groups.
 28. A compound according toclaim 27 wherein R₈ is a group of the general formula (III): ##STR31##wherein R₄ and R₅, which may be the same or different, each represents ahydrogen atom or a hydroxyl group provided that the both are nothydroxyl groups, m represents an integer of 1 through 4, and nrepresents an integer of 0 through
 2. 29. A compound according to claim26 of the general formula (X): ##STR32## wherein R₁₂ and R₁₃, which maybe the same or different, each represents a hydrogen atom or aprotective group, and R₁₄ represents a C1-10 alkyl group which may besubstituted.
 30. A compound according to claim 29 wherein the protectivegroup is an acyl or a substituted silyl group, and R₁₄ is a C1-10 alkylgroup substituted by one or more hydroxyl groups.
 31. A compound of thegeneral formula (XI): ##STR33## wherein R₁₅ and R₁₆, which may be sameor different, each represents a hydrogen atom or a protective group, andA₁ represents --CHOH-- or --CO--.
 32. A compound according to claim 31wherein the protective group is a substituted silyl group.
 33. Acompound according to claim 31 of the general formula (XII): ##STR34##wherein R₁₇ and R₁₈, which may be the same or different, each representsa hydrogen atom or a protective group, and A₂ represents --CHOH-- or--CO--.
 34. A compound of the general formula (XIII): ##STR35## whereinR₁₉ and R₂₀, which may be the same or different, each represents ahydrogen atom or a protective group, R₂₁ represents a C1-10 alkyl groupwhich may be substituted, and A₃ represents --CHOH-- or --CO--.
 35. Acompound according to claim 34 wherein the protective group is asubstituted silyl group, and R₂₁ is a C1-10 alkyl group substituted byone or more hydroxyl groups.
 36. A compound according to claim 35wherein R₂₁ is a group of the general formula (III): ##STR36## whereinR₄ and R₅, which may be the same or different, each represents ahydrogen atom or a hydroxyl group provided that the both are nothydroxyl groups, m represents an integer of 1 through 4, and nrepresents an integer through 0 to
 2. 37. A compound according to claim34 of the general formula (XIV): ##STR37## wherein R₂₂ and R₂₃, whichmay be the same or different, each represents a hydrogen atom or aprotective group, R₂₄ represents a C1-10 alkyl group which may besubstituted, and A₄ represents --CHOH-- or --CO--.
 38. A process forpreparing a compound of the general formula (XVI): ##STR38## wherein R₂₅represents a C1-10 alkyl group which may be substituted by one or morehydroxyl groups, R₂₆ and R₂₇, which may be the same or different, eachrepresents a hydrogen atom or a protective group, and R₂₈ represents ahydrogen atom or a hydroxyl group, said process comprising the step ofsubjecting a compound of the general formula (XV): ##STR39## whereinR₂₅, R₂₆, R₂₇ and R₂₈ are as defined above, to a light irradiationreaction and a thermal isomerization reaction.
 39. A process forpreparing a compound of the general formula (VI): ##STR40## wherein R₆and R₇, which may be the same or different, each represents a hydrogenatom or a protective group, and R₈ represents a C1-10 alkyl group whichmay be substituted, said process comprising the step of reacting acompound of the general formula (IV): ##STR41## wherein R₆ and R₇ are asdefined above, with a compound of the general formula (V):

    R.sub.8 --SH                                               (V)

wherein R₈ is as defined above, under reducing conditions.
 40. A processfor preparing a compound of the general formula (IX): ##STR42## whereinR₉ and R₁₀, which may be the same or different, each represents ahydrogen atom or a protective group, and R₁₁ represents a C1-10 alkylgroup which may be substituted, said process comprising the step ofreacting a compound of the general formula (VII): ##STR43## wherein R₉and R₁₀ are as defined above, with a compound of the general formula(VIII):

    R.sub.11 --SH                                              (VIII)

wherein R₁₁ is as defined above, under basic conditions.